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.

There is growing interest in the role of children’s play in supporting children’s mental health. Children’s opportunitities for play vary according to the space available to them for play, with more adventurous play happening outdoors (Dodd et al., 2021). The area close to children’s home, such as the street outside their home, can provide an important play space but, with increasing traffic, there has been a decrease in the use of local streets for play over the past generation or two. At the same time we have seen significant increases in children’s mental health problems.

Our objectives were: 1) to examine how trends in street play have changed over time; 2) to examine how children’s self-reported wellbeing is associated with their use of streets for play; 3) to examine how adult mental health is associated with their childhood street play experiences.

Working in collaboration with Save the Children and Play England, we surveyed a nationally representative sample of 1000 children and young people aged 6-16 years, 1000 adults aged 18+ and 1000 parents of children aged 6-16 years about children’s play in their local area and their memories of play during their own childhood. All participants also completed measures of wellbeing (children) or mental health (adults). Participants were recruited from Great Britian.

We found striking differences in the use of streets and local areas for play. For example, across all adults, 62% told us that they regularly played out in their street or area close to home as a child. In contrast 27% of children told us that they regularly play out now. By breaking down the proportion of participants who said they regularly played in their street or local area by their age group, their is a clear decline in outdoor street play over the past 70 years. We asked children about their wellbeing using the Stirling Children’s Wellbeing Scale. Children who said that they regularly played out in their street had higher levels of positive emotion but this was only true for children under 13 years. Adults who told us that they regularly played out in their street or area close to their home as a child had better mental health as adults (lower scores on the K6). Similarly, adults who told us that there was freedom for children to go and explore in the neighbourhood they lived in as a child had better mental health as adults.

Taken together these findings suggest that being able to play in the street or area close to home is linked to wellbeing during childhood and early adolescence and further, that having these expriences during childhood may be beneficial for mental health into adulthood. This indicates that when considering how to support the development of good mental health we should keep in mind the importance of children’s opportunities for play and the role that access to their local enviornment plays in supporting play.

None Declared

An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.

An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.

Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).

A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

The high prevalence of mental distress among university students is gaining academic, policy and public attention. As the volume of research into student mental health increases, it is important to involve students to ensure that the evidence produced can translate into meaningful improvements.

For the first time, we consult UK students about their research priorities on student mental health.

This priority setting exercise involved current UK university students who were asked to submit three research questions relating to student mental health. Responses were aggregated into themes through content analysis and considered in the context of existing research. Students were involved throughout the project, including inception, design, recruitment, analysis and dissemination.

UK university students (N = 385) submitted 991 questions, categorised into seven themes: epidemiology, causes and risk factors, academic factors and work–life balance, sense of belonging, intervention and services, mental health literacy and consequences. Across themes, respondents highlighted the importance of understanding the experience of minority groups.

Students are interested in understanding the causes and consequences of poor mental health at university, across academic and social domains. They would like to improve staff and students’ knowledge about mental health, and have access to evidence-based support. Future research should take a broad lens to evaluate interventions; considering how services are designed and delivered, and investigating institutional and behavioural barriers to accessibility, including how this varies across different groups within the student population.

Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown.

We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion.

After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection.

The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.

A number of strategies used to regulate positive affect (i.e. dampening and positive rumination) have been identified as having particular relevance to hypomanic personality (a proxy measure of mania risk). However, previous findings have been mixed and it is suggested that this may be the result of lack of consideration of the context in which emotion regulation (ER) is occurring.

This study aimed to investigate (a) if use of specific ER strategies predicts mood across social- and goal-related contexts, and (b) if the relationship between hypomanic personality and mood is moderated by greater use of ER strategies.

One hundred and seventy-four participants (mean age 20.77 years, SD = 2.2) completed an online survey assessing (i) hypomanic personality, (ii) self-reported tendencies to use ER strategies for positive emotion, (iii) tendencies to use these strategies in response to both high- and moderate-intensity positive affect in personally generated social- and goal-related contexts, and (iv) current affect.

Trait use of ER strategies was more predictive of hypomanic personality and mood symptoms than context-specific measures; however, this relationship did not hold up for hypomanic personality and mood symptoms when accounting for current affect. Trait dampening was predictive of low mood symptoms but did not moderate the relationship between hypomanic personality and low mood.

While trait measures of ER were more predictive of mania risk and mood symptoms than context-specific measures, further work is needed using experience sampling methods in order to capture the regulatory processes individuals are using in particular contexts, in real-time.

The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).

This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.

In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).

Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

To evaluate total usual intakes and biomarkers of micronutrients, overall dietary quality and related health characteristics of US older adults who were overweight or obese compared with a healthy weight.

Cross-sectional study.

Two 24-h dietary recalls, nutritional biomarkers and objective and subjective health characteristic data were analysed from the National Health and Nutrition Examination Survey 2011–2014. We used the National Cancer Institute method to estimate distributions of total usual intakes from foods and dietary supplements for eleven micronutrients of potential concern and the Healthy Eating Index (HEI)-2015 score.

Older adults aged ≥60 years (n 2969) were categorised by sex and body weight status, using standard BMI categories. Underweight individuals (n 47) were excluded due to small sample size.

A greater percentage of obese older adults compared with their healthy-weight counterparts was at risk of inadequate Mg (both sexes), Ca, vitamin B6 and vitamin D (women only) intakes. The proportion of those with serum 25-hydroxyvitamin D < 40 nmol/l was higher in obese (12 %) than in healthy-weight older women (6 %). Mean overall HEI-2015 scores were 8·6 (men) and 7·1 (women) points lower in obese than in healthy-weight older adults. In addition, compared with healthy-weight counterparts, obese older adults were more likely to self-report fair/poor health, use ≥ 5 medications and have limitations in activities of daily living and cardio-metabolic risk factors; and obese older women were more likely to be food-insecure and have depression.

Our findings suggest that obesity may coexist with micronutrient inadequacy in older adults, especially among women.

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.

The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.

There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.

These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.