Clinical guidelines for personality disorder emphasise the importance of patients being supported to develop psychological skills to help them manage their symptoms and behaviours. But where these mechanisms fail, and hospital admission occurs, little is known about how episodes of acutely disturbed behaviour are managed.

To explore the clinical characteristics and management of episodes of acutely disturbed behaviour requiring medication in in-patients with a diagnosis of personality disorder.

Analysis of clinical audit data collected in 2024 by the Prescribing Observatory for Mental Health, as part of a quality improvement programme addressing the pharmacological management of acutely disturbed behaviour. Data were collected from clinical records using a bespoke proforma.

Sixty-two mental health Trusts submitted data on 951 episodes of acutely disturbed behaviour involving patients with a personality disorder, with this being the sole psychiatric diagnosis in 471 (50%). Of the total, 782 (82%) episodes occurred in female patients. Compared with males, episodes in females were three times more likely to involve self-harming behaviour or be considered to pose such a risk (22% and 70% respectively: p < 0.001). Parenteral medication (rapid tranquillisation) was administered twice as often in episodes involving females than in males (64 and 34% respectively: p < 0.001).

Our findings suggest that there are a large number of episodes of acutely disturbed behaviour on psychiatric wards in women with a diagnosis of personality disorder. These episodes are characterised by self-harm and regularly prompt the administration of rapid tranquillisation. This has potential implications for service design, staff training, and research.

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

The migratory phase is a critical time for Fasciola hepatica as it must locate, penetrate and migrate through the alimentary tract to the liver parenchyma whilst under attack from the host immune response. Here, scanning and transmission electron microscopy were used to monitor the in vitro effects of sera (with, and without, complement depletion) on F. hepatica newly excysted juveniles (NEJs) and flukes recovered at 7, 35, 70 and 98 days post infection (dpi) from the liver and bile ducts of rats. Test sera were from these F. hepatica-infected rats. A F. hepatica NEJ-specific rabbit antiserum was also used. All fluke stages demonstrated release of the tegumental glycocalyx and microvesicles and intense activity within the tegumental syncytium characterized by eccrine secretion of T-0/T-1/T-2 secretory bodies with subsequent microvillar formation and shedding of microvesicles from the apical plasma membrane. Exposure of both NEJs and 35 dpi flukes to 35 and 70 dpi rat sera produced significant amounts of eccrine-derived secretory material and putative attached immunocomplex. Rabbit anti-F. hepatica NEJ-specific antiserum produced similar responses at the NEJ tegument, including binding of putative immunocomplex to the surface, but with additional blistering of some regions of the apical plasma membrane. Our data suggest that immune sera stimulates multiple interrelated secretory mechanisms to maintain the integrity of the tegumental barrier in response to immune attack. Concurrent release of microvesicles may also serve to both divert the immune response away from the fluke itself and permit delivery of immunomodulatory cargo to immune effector cells.

Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Managing clinical trials is a complex process requiring careful integration of human, technology, compliance, and operations for success. We collaborated with experts to develop a multi-axial Clinical Trials Management Ecosystem (CTME) maturity model (MM) to help institutions identify best practices for CTME capabilities.

A working group of research informaticists was established. An online session on maturity models was hosted, followed by a review of the candidate domain axes and finalization of the axes. Next, maturity level attributes were defined for min/max levels (level 1 and level 5) for each axis of the CTME MM, followed by the intermediate levels. A REDCap survey comprising the model’s statements was then created, and a subset of working group members tested the model by completing it at their respective institutions. The finalized survey was distributed to all working group members.

We developed a CTME MM comprising five maturity levels across 11 axes: study management, regulatory and audit management, financial management, investigational product management, subject identification and recruitment, subject management, data, reporting analytics & dashboard, system integration and interfaces, staff training & personnel management, and organizational maturity and culture. Informaticists at 22 Clinical and Translational Science Award hubs and one other organization self-assessed their institutional CTME maturity. Respondents reported relatively high maturity for study management and investigational product management. The reporting analytics & dashboard axis was the least mature.

The CTME MM provides a framework to research organizations to evaluate their current clinical trials management maturity across 11 axes and identify areas for future growth.

Inappropriate diagnosis and treatment of urinary tract infections (UTIs) contribute to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure uses a standard definition of asymptomatic bacteriuria (ASB) and was validated in large hospitals. Critical access hospitals (CAHs) have different resources which may make ASB stewardship challenging. To address this inequity, we adapted the ID-UTI metric for use in CAHs and assessed the adapted measure’s feasibility, validity, and reliability.

Retrospective observational study

10 CAHs

From October 2022 to July 2023, CAHs submitted clinical information for adults admitted or discharged from the emergency department who received antibiotics for a positive urine culture. Feasibility of case submission was assessed as the number of CAHs achieving the goal of 59 cases. Validity (sensitivity/specificity) and reliability of the ID-UTI definition were assessed by dual-physician review of a random sample of submitted cases.

Among 10 CAHs able to participate throughout the study period, only 40% (4/10) submitted >59 cases (goal); an additional 3 submitted >35 cases (secondary goal). Per the ID-UTI metric, 28% (16/58) of cases were ASB. Compared to physician review, the ID-UTI metric had 100% specificity (ie all cases called ASB were ASB on clinical review) but poor sensitivity (48.5%; ie did not identify all ASB cases). Measure reliability was high (93% [54/58] agreement).

Similar to measure performance in non-CAHs, the ID-UTI measure had high reliability and specificity—all cases identified as ASB were considered ASB—but poor sensitivity. Though feasible for a subset of CAHs, barriers remain.

To determine whether differences exist in antibiotic prescribing for respiratory infections in pediatric urgent cares (PUCs) by patient race/ethnicity, insurance, and language.

Multi-center cohort study.

Nine organizations (92 locations) from 22 states and Washington, DC.

Patients ages 6 months–18 years evaluated April 2022–April 2023, with acute viral respiratory infections, otitis media with effusion (OME), acute otitis media (AOM), pharyngitis, community-acquired pneumonia (CAP), and sinusitis.

We compared the use of first-line (FL) therapy as defined by published guidelines. We used race/ethnicity, insurance, and language as exposures. Multivariable logistic regression models estimated the odds of FL therapy by group.

We evaluated 396,340 ARI encounters. Among all encounters, 351,930 (88.8%) received FL therapy (98% for viral respiratory infections, 85.4% for AOM, 96.0% for streptococcal pharyngitis, 83.6% for sinusitis). OME and CAP had the lowest rates of FL therapy (49.9% and 60.7%, respectively). Adjusted odds of receiving FL therapy were higher in Black Non-Hispanic (NH) (adjusted odds ratio [aOR] 1.53 [1.47, 1.59]), Asian NH (aOR 1.46 [1.40, 1.53], and Hispanic children (aOR 1.37 [1.33, 1.41]), compared to White NH. Additionally, odds of receiving FL therapy were higher in children with Medicaid/Medicare (aOR 1.21 [1.18–1.24]) and self-pay (aOR 1.18 [1.1–1.27]) compared to those with commercial insurance.

This multicenter collaborative showed lower rates of FL therapy for children of the White NH race and those with commercial insurance compared to other groups. Exploring these differences through a health equity lens is important for developing mitigating strategies.