This exploratory study examined baseline characteristics modifying treatment effects on paranoia in individuals diagnosed with schizophrenia spectrum disorders following a 10-session virtual reality-based cognitive behavioral therapy for psychosis (VR-CBTp) or standard CBTp.

All participants in the FaceYourFears trial were included (n=254; CBTp n=128; VR-CBTp n=126). General linear and logistic regression models examined baseline variables associated with end-of-treatment paranoia. In covariate analyses, regression coefficients quantified associations across treatments. In moderation analyses, interaction terms (randomization x moderator) were tested, with corresponding regression coefficients estimated and assessed at the 25th (low), 50th (medium), and 75th (high) percentiles of continuous variables.

Across treatments, higher baseline avolition, safety behavior, delusion severity, and cognitive biases were associated with end-of-treatment paranoia. Moderation analyses revealed interactions for avolition, delusion severity, and negative other-beliefs. Although avolition and delusion severity were associated with poorer outcomes overall, individuals with high avolition and those with moderate-to-high delusion severity improved more in VR-CBTp than CBTp, whereas participants with lower delusion severity showed better outcomes in CBTp. No demographic (age, gender, education, and occupation) or other clinical characteristics (diagnosis, paranoia, social anxiety, depression, anhedonia, total negative symptoms, functioning, core beliefs, or interpersonal trauma) were significantly associated with outcome.

This exploratory study generates hypotheses for future research, including VR-CBTp’s potential to engage individuals with high avolition. Given the modest effects and largely nonsignificant findings, both CBTp and VR-CBTp appear suitable for a wide range of individuals with paranoia, highlighting the importance of considering patient preferences.

In Belgium, the Ministry of Health is responsible for the medical-psychosocial disaster care. One of the tasks is registering all those affected, wounded, and not-wounded. The evaluation of the Brussels Bombings (2016) showed that registration, collecting, processing, and disseminating data about those affected was difficult and became almost impossible in complex multi-site incidents.

This was the start of the Belgian Incident Tracking System (BITS) project. This system now collects, processes, and generates data on persons involved in an emergency situation. It traces and identifies those affected throughout both the medical and the psychosocial chain in a simple way.

Each relief worker can, based on their specific profile, complete the pathway and file of those affected step by step, through a mobile or web-based application, online and offline. This applies to the relief workers who are dispatched to the incident, the advanced medical units, the hospitals to which the injured are taken, and all the relief workers in the reception centers.

With BITS, psychosocial workers in a call center or at a reception center can look up missing persons within the relief chain. If the missing person is not found, a thorough registration of the search query is filed. This data can contribute to the identification of unknown persons, those seriously injured/unconscious, or deceased. For those who leave the scene without seeking help. BITS will enable an online “I Am Safe” counter.

Finally, a wide variety of lists, according to European privacy regulations, can be generated and shared with partners within a crisis center or with actors responsible for the aftercare. Whereas BITS is in production and is being used in incidents right now, the developments are still ongoing, including lessons learned after every exercise and/or incident.

Slovenia has engaged with Health Technology Assessment (HTA) for over two decades, but its system remains fragmented and underdeveloped. Until recently, responsibilities for evaluating health technologies were dispersed across multiple institutions without a central coordinating body or standardized methodology. Medicinal products have been subject to structured evaluation through the Health Insurance Institute of Slovenia, while other health technologies, including medical devices, diagnostics, and preventive interventions, have followed less consistent pathways under the Ministry of Health. The adoption of the European Union Health Technology Assessment Regulation), entering into force in January 2025, has provided new impetus for reform, requiring Slovenia to designate a national HTA body to participate in joint clinical assessments and align national processes with EU standards.

A mixed-methods analysis combining a narrative overview of HTA in Slovenia with findings from two multi-stakeholder workshops held in 2025. These workshops, which convened Slovenian and international experts, policymakers, clinicians, and patient representatives, explored opportunities and challenges for developing a robust HTA framework.

Key findings highlight the need to strengthen methodological capacity, introduce systematic stakeholder engagement, ensure transparency, and integrate real-world evidence into decision-making. Particular emphasis was placed on expanding HTA to medical devices, diagnostics, and digital health technologies, and on anticipating future innovations such as artificial intelligence.

Slovenia now stands at a pivotal juncture. Establishing a central HTA body with a clear legal mandate, building national expertise, and leveraging regional and European collaboration is essential to creating a transparent, evidence-based, and patient-centred HTA system.

New technologies are being developed in a context of scarcity. Health technology assessment (HTA) aims to support decision makers in providing equitable and affordable access to effective innovations. This study aims to summarize the policy-related findings of a Horizon2020 project on innovating HTA methods and discuss their implications for the governance of HTA in Europe.

A thematic analysis of policy-oriented papers (n = 18) from the Next Generation Health Technology Assessment (HTx) project was carried out to summarize challenges and solutions. Subsequently, via an online survey and in a 2-day meeting, European and global stakeholders (n = 21) were invited to comment on these solutions and to prioritize future strategies.

Reported challenges included a lack of access to standardized data, differences in evidentiary needs, existing policy structures, and a lack of capacity and knowledge. Suggested solutions were capacity building, national and international dialogues, standardization, and increased European collaboration. Stakeholders had different expectations with respect to the likely success of these solutions.

Innovation of HTA requires alignment of evidentiary needs through dialogues, standardization through increased European collaboration, and capacity building. However, without additional investments in personnel capacity, HTA agencies must still prioritize some activities at the expense of others. Furthermore, although European collaboration is important, global alignment might be required to enforce standardization.

Evidence regarding the effects of antipsychotic medication on cognitive functioning after a first-episode psychosis (FEP) remains inconclusive. This study examined whether dopamine D2 receptor occupancy, affinity, and antipsychotic dose are related to cognitive functioning in people in remission from FEP.

278 remitted FEP participants from the HAMLETT-trial were included. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia, 3–6 months after remission. D2 receptor occupancy was estimated based on antipsychotic type and dose. Antipsychotics were categorized into partial agonists, or antagonists with high or low D2 receptor affinity. Linear regression analyses were performed with inverse probability of treatment weighting to control for differences in characteristics between groups.

D2 receptor occupancy was negatively related to global cognition (β = −0.18), verbal fluency (β = −0.22), and attention and processing speed (β = −0.17, all p < 0.003). The interaction between daily dose and D2 receptor affinity category was significant for global cognition (p = 0.0046) and working memory (p = 0.0019), but not for verbal fluency after correction for multiple testing (p = 0.029). Interactions showed that higher daily dose was related to lower cognitive functioning, with significantly stronger negative effects in high-affinity antagonists compared to other antipsychotics.

The current findings underscore the importance of antipsychotic D2 receptor occupancy and affinity for cognitive functioning and suggest better cognitive functioning in users of partial agonists and low D2 receptor affinity antipsychotics. This can be important when selecting antipsychotics for individuals with FEP.

Tobacco smoking is highly prevalent in patients with psychosis, who also often experience negative affect (NA) and stress. The relationship between these factors remains unclear in this population. We aimed to investigate everyday life associations in 158 patients with psychosis, 136 unaffected siblings, and 117 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study with Experience Sampling Method measurements.

Generalized linear mixed models were used to evaluate across time and within-subject associations. Across time analyses investigated the relationship between smoking status and overall NA and stress. Within-subject analyses assessed whether smoking between two measurements (t−1 and t0) was associated with changes in NA and stress at the measurement after smoking a cigarette (t0) and at the subsequent measurement (t+1).

Across assessments, smoking status was initially associated with NA in patients (B=0.26, p=0.036), but this association disappeared after controlling for psychotic symptoms and cannabis use. Within-subject analyses in smokers showed a decrease in NA in patients after smoking (t0: −0.23, p=0.016), which remained significant after correcting for confounders (t0: −0.20, p=0.015). Siblings showed a decrease in NA (t0: −0.22, p=0.009), also after controlling for confounders (t0: −0.14, p=0.018). No time-lagged effect was found at t+1 after correction for subsequent smoking.

Overall smoking behavior was not associated with NA in patients with psychosis. In the short term, smoking in the daily life context is associated with a reduction in NA in people vulnerable to psychosis, possibly due to alleviation of withdrawal symptoms, which may complicate smoking cessation.

Low self-esteem is an important and potentially modifiable risk factor for the development and outcome of psychotic disorders. The factors involved in low self-esteem in psychotic disorders are not yet fully understood. The current study aims to investigate the cross-sectional and longitudinal associations between (changes in) self-esteem and severity of psychotic symptoms, internalized stigma, negative reaction to antipsychotics, personal recovery, childhood bullying, childhood trauma, and social support in symptomatically remitted first-episode psychosis (FEP) patients.

Data from the ongoing longitudinal Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study were used. Participants were in symptomatic remission for 3–6 months after the FEP. Cross-sectional associations (N = 299) were investigated through Pearson’s correlations, and longitudinal changes (N = 238) were investigated via linear regressions with inverse probability weighting.

Cross-sectionally, we found that lower self-esteem was related to higher severity of symptoms, higher internalized stigma, higher childhood trauma (specifically emotional neglect), higher childhood bullying, more negative side effects of antipsychotic medication, lower personal recovery, and lower social support. Longitudinally, contrary to our hypothesis, we found that higher baseline internalized stigma, higher childhood trauma (specifically emotional abuse), and a higher baseline negative subjective reaction to antipsychotics predicted an increase in self-esteem after 6 months. Furthermore, a decrease in psychotic symptoms, internalized stigma, and negative subjective reaction to antipsychotics, and an increase in social support predicted an increase in self-esteem.

Early intervention programs for psychotic disorders should target factors related to changes in self-esteem. This might improve self-esteem and thereby promote recovery.

Spatial neglect is a heterogeneous post-stroke disorder with subtypes differing in reference frames, processing stages, and spatial domains. While egocentric peri-personal neglect recovery has been studied, recovery trajectories of allocentric peri-personal visuospatial and personal neglect remain unclear. This study investigated recovery time courses of egocentric and allocentric peri-personal visuospatial and personal neglect during the first 12 weeks post-stroke; whether initial severity predicts recovery and defines distinct patient clusters; and how subtypes interrelate over time.

Forty-one first-ever stroke patients were evaluated at weeks 3, 5, 8, and 12 post-stroke using the Broken Hearts Test, Line Bisection Test, Visuospatial Search Time Test, and Fluff Test. Recovery was analyzed using linear mixed models, clustering with Gaussian finite mixture models, and interrelationships using Spearman correlations.

Significant improvements occurred in egocentric and allocentric peri-personal visuospatial and personal neglect, primarily between weeks 3 and 5, followed by a plateau. The Line Bisection Test detected no changes. Higher initial severity predicted greater residual impairment. Cluster analysis identified near-normal, mild, and moderate-to-severe baseline subgroups with distinct recovery trajectories. Moderate-to-good correlations (ρ = 0.33 – 0.55) emerged between egocentric and allocentric neglect at week 3 and when timepoints were pooled.

Neglect improved mainly between weeks 3 and 5 after which recovery plateaued, mirroring motor and language recovery and suggesting a shared time-limited window. Initial severity was a determinant of recovery, highlighting the value of early severity stratification to monitor and support recovery potential after stroke. As subtypes are distinctive, assessment should include multiple neglect tests.

Since 2019 the Dutch National Healthcare Institute has operated a coverage with evidence development (CED) program for specific products with insufficient evidence of their clinical benefit: orphan medicinal products (OMPs), medicines with conditional marketing authorization (CMA), and medicines with marketing authorization under exceptional circumstances (AEC). The objective of this study is to give an overview of this program and reflect on learnings, challenges, and opportunities.

This study is a narrative policy review of the Dutch CED program and describes the different phases and stakeholder involvement. Additionally, an overview of the medicines included in the CED program is presented and put in an international perspective.

The CED program consists of four phases: candidate prescreening, research protocol drafting, signing of process agreement and financial agreement, and controlled access. Stakeholders are involved intensively throughout the process. Since 2019, six medicines have entered the program. The program is used to fill different evidence gaps for various types of medicines and indications. In other countries, these medicines are often included in restricted reimbursement programs.

The CED program is gathering clinical effectiveness data while providing patient access to OMPs, CMA, and AEC products. Important facilitating factors for the program were identified, including the involvement of all stakeholders, the only-in-research approach of data gathering, and the case-by-case evidence generation requirements and duration. Continuous evaluation is needed as the program does not yet include the expected number of medicines, and no conclusion can be drawn so far on the usefulness of the data collection.

Evidence on psychological side effects (PSEs) of antipsychotic medication after remission from first-episode psychosis (FEP), and their momentary impact on daily life, is limited. This study examined how Dopamine-2 (D2) affinity and antipsychotic dosage relate to momentary PSEs.

This ecological momentary assessment (EMA) study included baseline data from 56 participants in the ongoing Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment (HAMLETT) trial. Momentary mental states indicative of reduced affect intensity, stability, and variability, as well as avolition and mental fatigue, were assessed 10×/day for eight days (N = 3,005 data points). Since these PSEs may result from D2-receptor actions, antipsychotics were classified by receptor affinity and mechanism of action. Multilevel mixed-effects regression models examined serial cross-sectional associations between D2 affinity or dosage and concurrent PSEs, both overall and separately for mornings, daytimes, and evenings.

Higher antipsychotic dosages were associated with reduced affect variability (Beta [B] = −1.40 [95% confidence interval [CI]: −2.52; −0.29]) and decreased positive affect stability (B = 0.23 [95% CI: 0.04; 0.42]) and intensity (B = −1.11 [95% CI: −1.97; −0.24]). The latter was also associated with the use of high-affinity D2 antagonists versus partial D2 agonists (B = 12.98 [95% CI: 2.43; 23.53]) and versus low-affinity D2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]). Other PSEs were not associated with D2 affinity/dosage. Results were relatively consistent across daytimes.

Higher antipsychotic dosage and high-affinity D2 antagonists were associated with decreased positive affect after remission from FEP, which may partly drive the frequently reported blunting of emotional experience.