By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.

A PubMed literature search covering the past 30 years was conducted using keywords such as “5-HT2A receptor,” “psychedelics,” “immune system,” and “HPA axis.” Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.

Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.

Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

As cancer incidence and survival rates rise, caregivers responsible for providing diverse support face increased burden and reduced quality of life (QoL). Although research on web-based interventions for this group is expanding, the impact of these interventions on caregiver burden and QoL remains unclear. This study aims to investigate the effects of web-based interventions on the caregiver burden and QoL of caregivers of patients with cancer.

Searches were conducted in PubMed, Web of Science, Cochrane Library, CINAHL, Embase, and PsycINFO from database inception to 10 June 2024. Two reviewers independently assessed each study and extracted data. The risk-of-bias in the studies was evaluated using Cochrane’s Risk-of-Bias tool for randomized controlled trials. The intervention effects were calculated using R package Meta version 4.0.3, utilizing standardized mean differences (SMD; Hedge’s ĝ) to calculate pooled effect sizes with 95% confidence intervals (CI). Publication bias assessment and sensitivity analysis were conducted to ensure the robustness of the results.

We reviewed 13 randomized controlled trials; our analysis indicated a small effect size of web-based interventions on caregiver burden (SMD = −0.19, 95% CI: −0.36 to −0.01). However, sensitivity analysis concluded that the effect was very small or nearly absent. Additionally, there was no statistically significant effect on QoL (SMD = 0.15, 95% CI: −0.05 to 0.36).

Web-based interventions did not significantly reduce caregiver burden or improve caregivers’ QoL. To improve caregiver burden and QoL in the future, comprehensive and tailored web-based interventions for this population are needed.

Anxiety and depression in epilepsy are common and impactful. Screening with validated measures at every epilepsy visit is a quality measure, yet screening remains limited due to time constraints.

This study aimed to develop an implementation strategy for anxiety and depression screening at an epilepsy center and evaluate it in a pre-post design with RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Guided by the Capability, Opportunity, Motivation-Behavior behavior change wheel framework, the strategy incorporated electronic health record tools and support staff activation of electronic screeners during visit check-in. Outcomes were evaluated over five months post-implementation and compared with two 3-month pre-implementation timeframes.

Post-implementation, 29.2% of 943 visits met the anxiety and depression screening quality measure, a significant increase from 12.6% immediately pre-implementation (p < 0.0001) and 6.28% before any screening interventions (p < 0.0001). Patients who completed electronic screeners post-implementation were younger than non-completers (mean 39.3 vs. 43.4 years, p = 0.001) and more likely to be white than other race/ethnicity categories (p = 0.002). There was substantial variability in screening rates among clinic staff (0–80% for support staff, 10.1–55.3% for providers), with higher screening among neurology support staff than temporary staff. Only 0.23% of post-implementation visits had screeners initiated but left incomplete. A shift to virtual visits during COVID-19 complicated Maintenance.

This framework-based implementation strategy effectively increased screening rates by epilepsy specialists, though challenges remain, including variability across clinic team members and lower reach among older and non-white patients. This study describes a feasible strategy for epilepsy centers to use for improved performance on an American Academy of Neurology quality measure (depression and anxiety screening for patients with epilepsy).

To compare rates of clinical response in children with Clostridioides difficile infection (CDI) treated with metronidazole vs vancomycin.

Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2–17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response.

One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response (P = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin (P = 0.105).

In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.

Plastics in the environment have moved from an “eye-sore” to a public health threat. Hospitals are one of the biggest users of single-use plastics, and there is growing literature looking at not only plastics in the environment but health care’s overall contribution to its growth.

This study was a retrospective review at a 411-bed level II trauma hospital over 47 months pre and post the last wave of COVID-19 affecting this hospital. Deidentified data were gathered: daily census in the emergency department, hospital census, and corresponding number of admitted COVID-19 patients. Additionally, for the same time frame, personal protective equipment (PPE) supply purchases and gross tonnage of nonhazardous refuse were obtained.

There was a large increase in PPE purchased without a significant change in gross tonnage of weight of trash.

PPE is incredibly important to protect health care workers. However, single-use plastic is not sustainable for the environment or public health. Understanding the full effect of the pandemic on hospital waste production is critically important as health care institutions focus on strategies to decrease their carbon footprint and increase positive impacts on public health and the environment.

In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825

The prevalence of schizophrenia is relatively low, yet increasing globally, and the disorder imparts a substantial burden of disease on both individuals and health systems. With regard to schizophrenia treatments, including long-acting injectable antipsychotics (LAIs), social media listening provides a unique source of insight into the experiences and perceptions of healthcare professionals (HCPs), patients, and caregivers who live with and manage this disorder daily.

To gain insight into HCP and patient/caregiver perceptions of LAIs for the treatment of schizophrenia.

Publicly available online conversations in global English about LAIs for schizophrenia from May 2, 2022, to May 2, 2023, were analyzed. Posts were collected using customized search strings from social media analysis tools, including Talkwalker and Meltwater. Online forums, such as Reddit, were the main source for patient/caregiver conversations. Conversations among HCPs were examined using publicly available posts from Twitter about schizophrenia/LAIs. Random samples of posts on forums (100) and Twitter (100) were coded for primary topic, author type (patient, caregiver, or HCP), sentiment toward LAIs, and signs of LAI hesitancy. Additional topics in posts, such as barriers and benefits to LAI use, were also examined.

In the analyzed samples, some differences were observed between patients/caregivers (mostly patients) and HCPs (mostly psychiatrists) in lexicon, focus, and perspective. The most common terms for LAIs among patients/caregivers were “injection” or “shot,” while HCPs used the terms “LAIs” or “injectables.” The most frequent primary topic among patients/caregivers was treatment regimen, including impact of symptoms and side effects on quality of life. HCPs focused on drug efficacy, including broader health outcomes such as relapse, hospitalization, adherence, and mortality. Patients/caregivers expressed fewer positive sentiments (11% of posts) and more negative sentiments (35%) than HCPs (34% positive, 14% negative). Both groups noted reduced relapse and improved adherence among the top treatment benefits. Barriers to LAI use commonly cited by patients/caregivers included side effects and lack of effect on negative symptoms, while common barriers cited by HCPs included patient access/cost and limited knowledge around best prescribing practices. Treatment comparisons and/or switching were more commonly mentioned among patients/caregivers (51%) than HCPs (30%), suggesting a greater interest in optimizing treatment among patients. Patients/caregivers often compared individual LAIs with oral antipsychotics (OAs) or different LAIs, whereas it was more typical for HCPs to compare LAIs with OAs than to distinguish between different LAIs.

Based on social media posts, patients/caregivers and HCPs had different primary treatment goals/concerns and generally used different lexicons, which may affect communication. Overall, HCPs were more positive and less negative toward LAIs than patients/caregivers. Top benefits noted (relapse and adherence) were similar between groups, while top treatment barriers differed. These differences highlight the need to improve communication between patients/caregivers and HCPs in order to increase treatment satisfaction and potentially improve treatment outcomes.

Teva Branded Pharmaceutical Products R&D, Inc.

Long-acting injectable antipsychotics (LAIs) reduce relapses in schizophrenia; however, most healthcare professionals (HCPs) reserve LAIs for nonadherence to oral antipsychotics (OAs) or severe disease.

US HCPs were surveyed regarding attitudes and perceptions toward LAIs for schizophrenia and LAI selection preferences. Respondents were grouped by LAI use (high [≥31% of patients using LAIs], low [≤14% using LAIs]; mid not analyzed) and archetype based on response to, “Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?” (see responses below).

Respondents (106 high, 130 low LAI use) were distributed across early LAI use (n=123), severity-reserved (n=88), adherence-reserved (n=113), and LAI-hesitant (n=56) archetypes.

Across all groups, HCPs estimated OA nonadherence in their practice (21%– 32%) to be lower than for patients nationwide (50%– 56%). Overall, 27% were dissatisfied with their LAI:OA use ratio, most thinking their OA use was too high. In all groups, side effects/tolerability was ranked as most important when choosing an LAI and “preference for the molecule” was ranked least important. Overall, 71%– 77% of HCPs were somewhat/much more likely to use a particular LAI based on multiple injection site options, small/on par needle, and price, and 63%– 82% of HCPs were somewhat/much more likely to select an LAI dosed once monthly or less often compared with an LAI dosed once every 2 weeks (8%). HCPs with high LAI use or early LAI use archetype were more likely to disagree that managing patients with schizophrenia increased their stress (64% and 63% vs 27%-45%, P<.05 each) and/or left them feeling “burned out” (77% and 79% vs 50%– 64%, P<.05 each).

Compared with other groups, greater proportions with high LAI use or early LAI use archetype consistently read new LAI publications (18% and 19% vs 0%– 5%, P<.01) and were confident in key aspects of LAI treatment (ie, dosing, managing side effects, access; 67%– 74% and 59%– 70% vs 11%– 57%, P<.05 each).

HCPs with low LAI use estimated the proportion of patients who initially refuse LAIs to be higher (mean, 55%) than those with low LAI use (44%, P<.01); there were no differences among archetypes (49%– 54%). HCPs with high LAI use or early LAI use archetype were more likely to “use any means necessary to ensure that a patient is on an LAI” vs other groups (44% and 51% vs 5%– 22%, P<.01 each) or had used guardianship to assist with treatment (70% and 69% vs 32%– 56%, P<.05 each); greater proportions with high LAI use or early LAI use archetype strongly agreed it was “worth [their] time to resolve issues with the insurance company” (42% and 45% vs 16%– 30%, P<.05 each) and were confident they would be able to do so (23% and 20% vs 2%– 11%, P<.05 each). Greater proportions of HCPs with early LAI use archetype vs the severity-reserved archetype strongly agreed that they attempt to determine the patient’s/caregiver’s preferred role before involving them (43% vs 27%, P<.05) and encourage them to participate (72% vs 57%, P<.05) in shared decision-making.

Comparing HCPs with high LAI use or early LAI use archetype vs other groups, multiple factors (eg, attitudes, preferences, training, knowledge base) combine to influence LAI use. These results highlight considerations for developing educational materials to increase LAI use in this population.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.

The diffusion of digital health interventions (DHIs) requires agreement on a minimum information framework to define them. The ISPOR Digital Health (DH) Special Interest Group (SIG) developed the PICOTS-ComTeC framework based upon a systematic review and a Delphi study. It is an enriched version of the traditional PICOTS widely adopted in health technology assessment (HTA). ComTeC stands for communication, technology, and context.

The PICOTS-ComTeC is based upon a review that included the Shannon–Weaver model of communication, AHRQ Quality Measures, technology, geography, and the World Health Organization classification of DHIs followed by a Delphi panel. The development process adhered to the EQUATOR guidelines. The PICOTS-ComTeC aims to be a flexible and versatile tool tested on different DHIs. The results of the testing are discussed from the HTA perspective considering the tool’s additional value, utility for and applicability to HTA. The additional value is strictly linked to the actual need for a dedicated PICOTS for DHIs and its implications for HTA assessments of DHIs.

The PICOTS-ComTeC was tested internally and externally to the ISPOR DH-SIG on four DHIs for breast cancer surgery/management/patient education, one DHI for obesity, and one DHI for patients with heart failure. The testing phase demonstrated the level of detail required to use the tool, hitherto available evidence to cover all domains, and opened up discussion on implications of the PICOTS-ComTeC framework for HTA related activities (i.e., scoping, literature search, comparator selection). It emerged that there is a diffuse lack of homogeneity and details when DHIs are defined in the literature with significant implications for conducting appropriate HTAs.

The diffuse adoption of the PICOTS-ComTeC for patient-facing DHIs will promote a greater level of detail in order to define homogenous DHI groups. The implications for HTA range from the definition of relevant research questions to the selection of the most appropriate comparator so that assessments are geared to fulfill the needs of decision-makers.

Paediatric patients with heart failure requiring ventricular assist devices are at heightened risk of neurologic injury and psychosocial adjustment challenges, resulting in a need for neurodevelopmental and psychosocial support following device placement. Through a descriptive survey developed in collaboration by the Advanced Cardiac Therapies Improving Outcomes Network and the Cardiac Neurodevelopmental Outcome Collaborative, the present study aimed to characterise current neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices.

Members of both learning networks developed a 25-item electronic survey assessing neurodevelopmental and psychosocial care practices specific to paediatric ventricular assist device patients. The survey was sent to Advanced Cardiac Therapies Improving Outcomes Network site primary investigators and co-primary investigators via email.

Of the 63 eligible sites contacted, responses were received from 24 unique North and South American cardiology centres. Access to neurodevelopmental providers, referral practices, and family neurodevelopmental education varied across sites. Inpatient neurodevelopmental care consults were available at many centres, as were inpatient family support services. Over half of heart centres had outpatient neurodevelopmental testing and individual psychotherapy services available to patients with ventricular assist devices, though few centres had outpatient group psychotherapy (12.5%) or parent support groups (16.7%) available. Barriers to inpatient and outpatient neurodevelopmental care included limited access to neurodevelopmental providers and parent/provider focus on the child’s medical status.

Paediatric patients with ventricular assist devices often have access to neurodevelopmental providers in the inpatient setting, though supports vary by centre. Strengthening family neurodevelopmental education, referral processes, and family-centred psychosocial services may improve current neurodevelopmental/psychosocial care for paediatric ventricular assist device patients.