Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

On February 24, 2022, Russia invaded Ukraine, resulting in Europe’s largest refugee crisis since World War II. More than six million Ukrainians fled the country—half of these to Poland—and one-third of the population was internally displaced.

Border points became bottlenecks where fatalities were reported—people risked their lives in long queues and subzero temperatures.

This presentation focuses on experiential information obtained during a 17-week deployment of EMT Type 1 both at border points (fixed) and in northwestern Ukraine (mobile). Quantitative and qualitative data were obtained after deployment by online survey with 75 medical, logistical and interpreter volunteers.

Initial teams experienced extremely fluid demands and numerous challenges with security, team adherence to COVID-19 protocols, behavioral issues with less experienced volunteers, and collaboration with novel governmental and non-governmental partners to achieve objectives.

1. Deployment to a conflict setting requires adherence to the Incident Command System, with daily security briefings and structured handover between teams at the beginning of each deployment.

2. Strict adherence to well-defined protocols for the prevention and management of emerging infectious risks such as COVID-19 is necessary, along with contingency plans to isolate infected team members.

3. There is a need for standardized pre-deployment vetting, training and orientation of all volunteers—particularly team leaders.

4. Identification of international partners should start pre-deployment and remain a continuous process during deployment.

Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.

We examined a multi-ancestry cohort of women and men (n = 289) who presented to the emergency department (ED) after trauma. Blood DNA was collected at ED presentation, and EPIC DNA methylation arrays were used to assess four widely used metrics of epigenetic aging (HorvathAge, HannumAge, PhenoAge, and GrimAge). PTSD symptoms were evaluated longitudinally at the time of ED presentation and over the ensuing 6 months. Structural and functional neuroimaging was performed 2 weeks after trauma.

After covariate adjustment and correction for multiple comparisons, advanced ED GrimAge predicted increased risk for 6-month probable PTSD diagnosis. Secondary analyses suggested that the prediction of PTSD by GrimAge was driven by worse trajectories for intrusive memories and nightmares. Advanced ED GrimAge was also associated with reduced volume of the whole amygdala and specific amygdala subregions, including the cortico-amygdaloid transition and the cortical and accessory basal nuclei.

Our findings shed new light on the relation between biological aging and trauma-related phenotypes, suggesting that GrimAge measured at the time of trauma predicts PTSD trajectories and is associated with relevant brain alterations. Furthering these findings has the potential to enhance early prevention and treatment of posttraumatic psychiatric sequelae.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant nosocomial pathogen in the ICU. MRSA contamination of healthcare personnel (HCP) gloves and gowns after providing care to patients with MRSA occurs at a rate of 14%–16% in the ICU setting. Little is known about whether the MRSA isolates identified on HCP gown and gloves following patient care activities are the same as MRSA isolates identified as colonizing or infecting the patient.

From a multisite cohort of 388 independent patient MRSA isolates and their corresponding HCP gown and glove isolates, we selected 91 isolates pairs using a probability to proportion size (PPS) sampling method. To determine whether the patient and HCP gown or gloves isolates were genetically similar, we used 5 comparative genomic typing methods: phylogenetic analysis, spa typing, multilocus sequence typing (MLST), large-scale BLAST score ratio (LSBSR), and single-nucleotide variant (SNV) analysis.

We identified that 56 (61.5%) of isolate pairs were genetically similar at least by 4 of the methods. Comparably, the spa typing and the LSBSR analyses revealed that >75% of the examined isolate pairs were concordant, with the thresholds established for each analysis.

Many of the patient MRSA isolates were genetically similar to those on the HCP gown or gloves following a patient care activity. This finding indicates that the patient is often the primary source of the MRSA isolates transmitted to the HCP, which can potentially be spread to other patients or hospital settings through HCP vectors. These results have important implications because they provide additional evidence for hospitals considering ending the use of contact precautions (gloves and gowns) for MRSA patients.

Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS.

Self-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale – Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample).

Twenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms.

These analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.

Deliberative processes for health technology assessment (HTA) are intended to facilitate participatory decision making, using discussion and open dialogue between stakeholders. Increasing attention is being given to deliberative processes, but guidance is lacking for those who wish to design or use them. Health Technology Assessment International (HTAi) and ISPOR—The Professional Society for Health Economics and Outcomes Research initiated a joint Task Force to address this gap.

The joint Task Force consisted of fifteen members with different backgrounds, perspectives, and expertise relevant to the field. It developed guidance and a checklist for deliberative processes for HTA. The guidance builds upon the few, existing initiatives in the field, as well as input from the HTA community following an established consultation plan. In addition, the guidance was subject to two rounds of peer review.

A deliberative process for HTA consists of procedures, activities, and events that support the informed and critical examination of an issue and the weighing of arguments and evidence to guide a subsequent decision. Guidance and an accompanying checklist are provided for (i) developing the governance and structure of an HTA program and (ii) informing how the various stages of an HTA process might be managed using deliberation.

The guidance and the checklist contain a series of questions, grouped by six phases of a model deliberative process. They are offered as practical tools for those wishing to establish or improve deliberative processes for HTA that are fit for local contexts. The tools can also be used for independent scrutiny of deliberative processes.

Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.

In a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.

79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).

Patients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.

Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance.

We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours.

198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ).

The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach’s alpha = .93, avoidance Cronbach’s alpha = .94, within-situation Cronbach’s alpha = .93) and test–re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89).

The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.

A national survey characterized training and career development for translational researchers through Clinical and Translational Science Award (CTSA) T32/TL1 programs. This report summarizes program goals, trainee characteristics, and mentorship practices.

A web link to a voluntary survey was emailed to 51 active TL1 program directors and administrators. Descriptive analyses were performed on aggregate data. Qualitative data analysis used open coding of text followed by an axial coding strategy based on the grounded theory approach.

Fifty out of 51 (98%) invited CTSA hubs responded. Training program goals were aligned with the CTSA mission. The trainee population consisted of predoctoral students (50%), postdoctoral fellows (30%), and health professional students in short-term (11%) or year-out (9%) research training. Forty percent of TL1 programs support both predoctoral and postdoctoral trainees. Trainees are diverse by academic affiliation, mostly from medicine, engineering, public health, non-health sciences, pharmacy, and nursing. Mentor training is offered by most programs, but mandatory at less than one-third of them. Most mentoring teams consist of two or more mentors.

CTSA TL1 programs are distinct from other NIH-funded training programs in their focus on clinical and translational research, cross-disciplinary approaches, emphasis on team science, and integration of multiple trainee types. Trainees in nearly all TL1 programs were engaged in all phases of translational research (preclinical, clinical, implementation, public health), suggesting that the CTSA TL1 program is meeting the mandate of NCATS to provide training to develop the clinical and translational research workforce.

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.

This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.

We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.

We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia.

Electronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case–control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality.

We identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 μmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45–0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29–1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment.

In the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.