Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.

High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.

Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).

Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.

Primary youth mental health services in Australia have increased access to care for young people, yet the longer-term outcomes and utilisation of other health services among these populations is unclear.

To describe the emergency department presentation patterns of a help-seeking youth mental health cohort.

Data linkage was performed to extract Emergency Department Data Collection registry data (i.e. emergency department presentations, pattern of re-presentations) for a transdiagnostic cohort of 7024 youths (aged 12–30 years) who presented to mental health services. Outcome measures were pattern of presentations and reason for presentations (i.e. mental illness; suicidal behaviours and self-harm; alcohol and substance use; accident and injury; physical illness; and other).

During the follow-up period, 5372 (76.5%) had at least one emergency department presentation. The presentation rate was lower for males (IRR = 0.87, 95% CI 0.86–0.89) and highest among those aged 18 to 24 (IRR = 1.117, 95% CI 1.086–1.148). Almost one-third (31.12%) had an emergency department presentation that was directly associated with mental illness or substance use, and the most common reasons for presentation were for physical illness and accident or injury. Index visits for mental illness or substance use were associated with a higher rate of re-presentation.

Most young people presenting to primary mental health services also utilised emergency services. The preventable and repeated nature of many presentations suggests that reducing the ongoing secondary risks of mental disorders (i.e. substance misuse, suicidality, physical illness) could substantially improve the mental and physical health outcomes of young people.

Understanding premature mortality risk from suicide and other causes in youth mental health cohorts is essential for delivering effective clinical interventions and secondary prevention strategies.

To establish premature mortality risk in young people accessing early intervention mental health services and identify predictors of mortality.

State-wide data registers of emergency departments, hospital admissions and mortality were linked to the Brain and Mind Research Register, a longitudinal cohort of 7081 young people accessing early intervention care, between 2008 and 2020. Outcomes were mortality rates and age-standardised mortality ratios (SMR). Cox regression was used to identify predictors of all-cause mortality and deaths due to suicide or accident.

There were 60 deaths (male 63.3%) during the study period, 25 (42%) due to suicide, 19 (32%) from accident or injury and eight (13.3%) where cause was under investigation. All-cause SMR was 2.0 (95% CI 1.6–2.6) but higher for males (5.3, 95% CI 3.8–7.0). The mortality rate from suicide and accidental deaths was 101.56 per 100 000 person-years. Poisoning, whether intentional or accidental, was the single greatest primary cause of death (26.7%). Prior emergency department presentation for poisoning (hazard ratio (HR) 4.40, 95% CI 2.13–9.09) and psychiatric admission (HR 4.01, 95% CI 1.81–8.88) were the strongest predictors of mortality.

Premature mortality in young people accessing early intervention mental health services is greatly increased relative to population. Prior health service use and method of self-harm are useful predictors of future mortality. Enhanced care pathways following emergency department presentations should not be limited to those reporting suicidal ideation or intent.

Since 2013, the coverage of innovative and expensive drugs by the French National Health Insurance considers cost-effectiveness and budget impact, as assessed by the National Authority for Health (HAS) on the basis of an evaluation submitted by the firm. First CAR-T cell therapies were subject to economic evaluation in 2019 in France. We aim at describing the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel and the challenges these evaluations raised.

Primary evaluations were submitted by the firms to be reviewed by HAS. The final analyses were submitted to the Committee of Economic Evaluation and Public Health (CEESP), composed of independent economists, clinicians and patients’ representatives. The CEESP issued Opinions related to i) the methodological quality of economic evidence and ii) the cost-effectiveness and budget impact of the drugs under review.

The estimated incremental cost-utility ratio (ICUR) of tisagenlecleucel were rejected, being based on insufficient clinical evidence to estimate and extrapolate the long-term progression and to compare tisagenlecleucel with alternatives. Thus, the CEESP concluded that tisagenlecleucel was not proved cost-effective. The estimated ICUR of axicabtagene ciloleucel at 114,509EUR/QALY vs. chemotherapies was associated with an acceptable level of evidence despite being based on a frail indirect comparison and limited data on quality of life. In a context where France has no official cost-effectiveness threshold, the CEESP considered axicabtagene ciloleucel ICUR to be “very high” and questioned the collective acceptability of the claimed price.

The CEESP stressed that the main source of uncertainty surrounding the ICUR estimates of both drugs was related to the lack of hindsight on effectiveness, especially in terms of overall survival and safety.

The economic evaluation of CAR-T cell therapies highlights the sources of uncertainty underlying the decision and the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for the uncertainty, and effective collection of relevant post-marketing data.

This quality improvement project aimed to assess the adherence of a hospital psychiatric liaison team's documentation of assessments to the Psychiatric Liaison Accreditation Network (PLAN) standards framework; to identify areas of improvement; to identify barriers to and improve adherence.

Data were extracted from 27 randomly selected patient assessments from 01/07/2020 to 31/08/2020 and then 27 assessments from 01/10/2020 to 30/11/2020 for re-audit.

Quantitative data was collected by calculating the percentage of assessments which documented each specific aspect of PLAN standards.

Qualitative data including attitudes specifically towards writing to patients was gathered from 1:1 discussions with members of staff.

Interventions between rounds of audit:

Presentation of results of 1st data collection to team in November 2020 followed by discussion

Emailed instructions to create a template based on PLAN standards for assessments to staff

Lobbied for Cerner access at liaison team office to facilitate use of above

Quantitative – overall improvements were seen in adherence to all aspects of documentation of assessments including collateral history (from 23% to 67%) past medical history (30% to 70%) and acknowledging the patient/carer perspective (46% to 74%). Some improvement was seen in offering written correspondence to patients (0% to 20%).

Qualitative – the majority of comments regarding writing to patients were positive, with no staff members opposing the standard (“it is best practice”, “should become a habit”). However, some barriers were identified including increased workload (“requires more editing”, “could take a lot more time”).

Team adherence to PLAN standards for documentation of assessments was improved through low intensity interventions. Overall adherence was high, however certain areas leave space for improvement. The audit facilitated conversations around writing to patients on discharge, both in the form of formal gathering of qualitative data and informal discussions between staff. Attitudes towards writing these letters were positive and some improvement was seen between audits. Ongoing audit activity aims to further improve adherence and monitor improvements.

Coordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.

In 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.

N=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.

The implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.

Supported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students.

An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health.

Twenty-two higher education institutions.

College students (n 17 686) enrolled at one of twenty-two participating universities.

Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04).

College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.

There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need.

We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up.

In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups.

CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.

To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.

Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.

A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).

The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.

Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Material and social environmental stressors affect mental health in adolescence. Protective factors such as social support from family and friends may help to buffer the effects of adversity.

The association of violence exposure and emotional disorders was examined in Cape Town adolescents.

A total of 1034 Grade 8 high school students participated from seven government co-educational schools in Cape Town, South Africa. Exposure to violence in the past 12 months and post-traumatic stress disorder (PTSD) symptoms were measured by the Harvard Trauma Questionnaire, depressive and anxiety symptoms by the Short Moods and Feelings Questionnaire and the Self-Rating Anxiety Scale.

Exposure to violence was associated with high scores on depressive (odds ratio (OR)=6.23, 95% CI 4.2–9.2), anxiety (OR=5.40, 95% CI 2.4–12.4) and PTSD symptoms (OR=8.93, 95% CI 2.9–27.2) and increased risk of self-harm (OR=5.72, 95% CI 1.2–25.9) adjusting for gender and social support.

We found that high exposure to violence was associated with high levels of emotional disorders in adolescents that was not buffered by social support. There is an urgent need for interventions to reduce exposure to violence in young people in this setting.