Nitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD).

We aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo.

In this randomised, active, placebo-controlled pilot trial, 40 participants with TRD were assigned either a 1-h inhalation of 50% nitrous oxide plus intravenous saline (n = 20) or a 1-h inhalation of 50% oxygen plus intravenous midazolam (0.02 mg/kg, up to 2 mg; n = 20) once weekly, for 4 weeks. Feasibility was assessed by examining rates of recruitment, withdrawal, adherence, missing data and adverse events. The main measure of clinical efficacy was the change in depression severity (Montgomery–Åsberg Depression Rating Scale (MADRS)) score from baseline to day 42.

The recruitment rate was 22.3% (95% CI 16.9–29.0). Withdrawal rates were 10% (95% CI 2.8–30.1) in both groups and adherence rates were 100.0% (95% CI 82.4–100) in the nitrous oxide group and 94.4% (95% CI 74.2–99.0) in the placebo group. There were no missing primary clinical outcome data in either group (0.0%, 95% CI 0.0–17.6). MADRS score changed by −20.5% (95% CI −39.6 to −1.3) in the nitrous oxide group and −9.0% (95% CI −22.6 to 4.6) in the placebo group. Nearly all adverse events were mild to moderate and transient.

The findings support the feasibility and necessity of conducting a full-scale trial comparing nitrous oxide and midazolam in patients with TRD.

Return of fear after successful exposure therapy for a phobia is a common clinical challenge. A previous study on mice demonstrated that the persistent attenuation of remote fear memories can be achieved by combining histone deacetylase inhibitors (HDACis) with fear-memory retrieval prior to extinction training.

To evaluate the translational potential of this approach, we conducted a randomized, double-blind, placebo-controlled trial. Forty-eight individuals with DSM-IV spider phobia received either HDACi valproic acid (VPA, 500 mg) or a placebo prior to the retrieval of fear memory, followed by exposure therapy in virtual reality.

No significant group difference was found in terms of behavioral change on the behavioral approach test at 3 months follow-up and baseline (primary outcome). However, the VPA group displayed significantly reduced fear in two self-report questionnaires related to spider phobia (Fear of Spiders Questionnaire; Spider Phobia Beliefs Questionnaire) as compared to the placebo group. No group differences were observed for psychophysiological indicators of fear.

The favorable impact of a single administration of VPA in combination with fear-memory retrieval prior to exposure therapy suggests that it might be an effective way to enhance symptom improvement at the subjective level in the treatment of phobias. Further studies need to investigate the conditions under which an improvement on the psychophysiological and behavioral levels can be achieved as well.

Numerous efforts are focused on building the clinical and translational research (CTR) workforce. Approaches to evaluate CTR initiatives are varied, and efforts often rely on research project-level outcomes. This article applies an evaluation tool to capture individual-level data.

The study used a novel Researcher Investment Tool (RIT) to measure researchers’ experience as well as perceptions of institutional support, including an analysis based on researcher characteristics. The study also evaluated the RIT based on common measures, including a bibliometric indicator, investigator status, and percent time dedicated to research.

The RIT was administered to researchers who received funding or targeted research support from a CTR initiative. Mean scores were assessed by RIT section, domains/sub-domains, and for each item. Mean scores per section were compared across researcher characteristics using t-tests, and associations between common measures and average domain scores were tested using linear regression.

Thirty researchers completed all RIT items. RIT domain scores ranged from a high mean of 4.0 for the research skills domain to a low mean of 2.6 for researcher productivity and community engagement domains. Analysis of indicators of commonly used measures across domains suggest that researchers with a higher bibliometric score had more advanced research skills, service to profession, research productivity, and research collaboration (p < .05). New investigators had lower perceptions of institutional support (p < .05).

As an evaluation tool, the RIT captures individual-level data that may help to determine key areas of strength and opportunities for growth of a CTR program.

Temporal arteritis (TA) is the most common vasculitis over age 50. Untreated, many patients will suffer blindness or stroke. Gold standard diagnosis is achieved by temporal artery biopsy. The aim of this study was to investigate the relevance of small vessel inflammation.

Our dataset was comprised of 72 temporal artery biopsies subjected to a blinded uniform re-examination paired with clinical data including demographics, history, physical examination and laboratory findings. Documented pathology variables included the presence or absence of TA, angiitis of vasa vasorum (AVV) and inflammation of small peri-adventitial vessels (small vessel vasculitis, SVV).

Clinical and pathological variables were subjected to multivariate analysis. In brief, 25% of cases were identified as TA, 20% as isolated AVV, 7% as isolated SVV and 5% as mixed isolated AVV/SVV, while 43% had no inflammation (NI). All cases of TA were accompanied by small vessel inflammation: 95% exhibited AVV with or without SVV, and 5% exhibited SVV alone, demonstrating a strong association between TA and small vessel inflammation. Of the 24 cases with isolated AVV/SVV, 26% received a clinical diagnosis of TA within one year in comparison to 13% of cases that had NI. Furthermore, isolated AVV/SVV was identified in 25% of patients with a high clinical probability for TA, 60% of whom acquired a diagnosis of TA on clinical grounds within one year of follow-up.

Our findings suggest that isolated AVV/SVV identifies a subgroup of patients with a higher risk of harboring or developing TA.

The purpose of this study is to examine the existing literature on end-of-life dream experiences and bucket list fulfillments among terminally ill individuals receiving hospice and/or palliative care.

A scoping review registered on Open Science Framework was conducted in accordance with the guidelines for Scoping reviews (PRISMA-ScR). An electronic search of literature was generated from EBSCO databases published until June 2024. Studies were included if they described and evaluated the effects of bucket lists and/or end-of-life wish fulfillment.

This review identified 2,234 studies, and 11 of these were included in the review. Four major themes were established using thematic content analysis: (1) impact on holistic well-being, (2) role of family in wish fulfillment, (3) cultivation of gratitude, and (4) collaborative leadership in wish fulfillment. In wish fulfillment, the results significantly pointed to the need for more intricate evaluation among patients and interventions that cover beyond the physical aspect.

Palliative and hospice care settings should work toward securing sustainable funding for structured wish-fulfillment programs to address existing accessibility gaps and further enhance the holistic nature of care in these settings. Wish-fulfillment interventions represent a powerful tool in enhancing dignity and holistic experiences for terminally ill patients. Future research efforts could strengthen programs ensuring every individual is able to achieve a sense of peace, fulfillment, and closure during their care trajectory.

Although life stressors are known risk factors for suicide, the specific stressor types that most strongly precipitate suicidal outcomes, and on what timescale, remain poorly understood. Based on existing theory, we investigated whether objectively rated interpersonal stressors, especially social and targeted rejection stressors, are proximally associated with increased likelihood of suicidal ideation and behavior.

Using an objectively rated contextual threat interview to assess stressful life events, and a timeline followback procedure for assessing suicide-related outcomes, we examined how the severity of four types of acute life events (i.e. non-interpersonal, interpersonal without social rejection, social rejection without targeted rejection, and targeted rejection) were temporally associated with the likelihood of same-day and next-day suicidal ideation and behavior over 16 months in 143 young adults (Mage = 25.27, SD = 4.65) with recent suicidal ideation or behavior.

After controlling for prior-day suicidal ideation and non-interpersonal stressors, daily within-person increases in interpersonal stressor severity were related to higher odds of same-day (but not next-day) suicidal ideation. Additionally, greater increases in targeted rejection severity were uniquely related to increased likelihood of both same-day and next-day suicidal behavior after controlling for prior-day suicidal behavior and other types of stressors.

Interpersonal stressors are strong, proximal risk factors for suicidal ideation and behavior, and these effects are particularly strong for targeted rejection life events. Clinicians should thus assess recent interpersonal and, especially, targeted rejection stressors when evaluating acute suicide risk, and may reduce such risk by helping patients stabilize and strengthen their social relationships.

Real-world evidence (RWE) is increasingly used to assess and make regulatory decisions on health technologies. However, its application in healthcare payer decision-making is less well-known.

The objectives of this study were to (i) review the recent literature on how RWE has been used by healthcare payers, (ii) highlight barriers that limit the use of RWE in payer decision making, and (iii) explore how RWE has been used in various funding arrangements between payers and manufacturers. The benefits of utilizing RWE are also discussed.

A scoping review was conducted on articles published between 2014 and 2025 in PubMed (Medline), OVID EMBASE, Cochrane Library, and ProQuest Dissertations and Theses Global. Eligible articles were those written in English that discussed the use of real-world evidence among healthcare payers/decision-makers for health technology reimbursement decisions.

Nineteen articles were selected for full-text review based on the inclusion criteria. The review highlighted payers’ interest in incorporating RWE into funding and reimbursement decisions to address uncertainty in the performance of new health technologies. However, a lack of standards for collecting, analyzing, and reporting RWE limits its use. Little is known about how RWE is used in reimbursement decisions since contractual arrangements between payers and manufacturers are confidential.

Although payers are interested in using RWE to inform funding and reimbursement decisions, there are concerns regarding the scientific rigor used to generate such evidence. Having more insight into the contractual arrangements between payers and manufacturers would help to better understand how RWE informs these agreements.

The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this may advise on the rate of receptor occupancy change that provokes the emergence of psychotic symptoms.

Exploring the relationship between psychotic symptoms and variations in plasma concentration (and calculated receptor occupancy) of long-acting injectable antipsychotics.

This longitudinal study monitored mental state variation within dosing cycles of people taking depot flupentixol and zuclopenthixol. The Positive and Negative Syndrome Scale (PANSS) monitored global mental state changes, and was stratified into domains according to a five-factor model. Plasma assays at maximal and minimal concentrations allowed prediction of striatal D2 occupancy from published data. We examined correlations between receptor occupancy and the emergence of psychotic symptoms.

Preliminary results from ten participants with psychotic disorders suggest that global mental state deterioration may correlate with increased rate of D2 occupancy reduction. Increased rate of D2 occupancy reduction led to deterioration in ‘positive’ (r = 0.637 [CI: 0.013, 0.904], P = 0.047) and ‘resistance’ (r = 0.726 [CI: 0.177, 0.930], P = 0.018) PANSS clinical domains at minimal concentrations. PANSS score differences were not related to absolute reduction in D2 occupancy.

Our novel observational study design has been demonstrated to be feasible and practicable. Faster reductions in D2 occupancy may increase the risk of increased positive psychotic symptoms and irritability. Slower reductions may minimise this effect. Further recruitment is required before this can be confirmed.