Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease.

BACKGROUND: It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with (i) stable PCa (sPCa) postprimary or salvage RT, (ii) progressing PCa (pPCa) post-RT, and (iii) de novo metastatic PCa (mPCa). METHODS: A cohort of 19 patients with diagnostic prostate biopsies (n = 6 sPCa, n = 5 pPCa, n = 8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3'RNA sequencing (3'RNAseq) (n = 19), nanoString analysis (n = 12), and Illumina 850k methylation (n = 8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes and methylated genomic regions (MGRs). RESULTS: Eighteen of 19 samples provided useable 3'RNAseq data. Principal component analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p < 0.0001) in an external cohort. CONCLUSIONS: 3'RNAseq, nanoString and 850k-methylation analyses are each achievable from historical FFPE diagnostic pretreatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .

Functional connectivity of amygdala subnuclei in PTSD: a narrative review.

While the amygdala is often implicated in the neurobiology of posttraumatic stress disorder (PTSD), the pattern of results remains mixed. One reason for this may be the heterogeneity of amygdala subnuclei and their functional connections. This review used PRISMA guidelines to synthesize research exploring the functional connectivity of three primary amygdala subnuclei, basolateral (BLA), centromedial (CMA), and superficial nuclei (SFA), in PTSD (N = 331) relative to trauma-exposed (N = 155) and non-trauma-exposed controls (N = 210). Although studies were limited (N = 11), preliminary evidence suggests that in PTSD compared to trauma-exposed controls, the BLA shows greater connectivity with the dorsal anterior cingulate, an area involved in salience detection. In PTSD compared to non-trauma-exposed controls, the BLA shows greater connectivity with the middle frontal gyrus, an area involved in attention. No other connections were replicated across studies. A secondary aim of this review was to outline the limitations of this field to better shape future research. Importantly, the results from this review indicate the need to consider potential mediators of amygdala subnuclei connectivity, such as trauma type and sex, when conducting such studies. They also highlight the need to be aware of the limited inferences we can make with such small samples that investigate small subcortical structures on low field strength magnetic resonance imaging scanners. Collectively, this review demonstrates the importance of exploring the differential connectivity of amygdala subnuclei to understand the pathophysiology of PTSD and stresses the need for future research to harness the strength of ultra-high field imaging to gain a more sensitive picture of the neural connectivity underlying PTSD.

Perspectives on technology - prostate cancer: is local anaesthetic transperineal prostate biopsy really better than transrectal biopsy?

For many years, transrectal ultrasound-guided (TRUS) prostate biopsies have been performed to establish a histological diagnosis of prostate cancer. This has been the recommended standard of care procedure, but has always carried risks, in particular the risk of post-procedural sepsis, and the associated antibiotic burden and risk of development of antibiotic resistance. Transperineal (TP) prostate biopsies performed under local anaesthetic (LA) have been proposed as a possible solution to these issues, with potentially lower infectious complications, and avoidance of need for antibiotic prophylaxis. The European Association of Urology produced guidance in 2023 with 'weak' recommendations in favour of LATP biopsy as a new standard of care, citing its safety profile. Both the National Institute for Health and Care Excellence in the UK, and the American Urological Association in the United States, have concluded for now that the body of evidence is inadequate and not offered a similar recommendation. We discuss the available evidence, pros and cons of each technique, and the status of current trials in the field. We believe that clinical equipoise remains necessary, given the disparity in national and international guidelines highlighting the need for large randomised controlled trials to answer the question: is LATP biopsy really better than TRUS biopsy?

Relationship between trauma, psychological distress and help-seeking among corrective service workers.

BACKGROUND: Corrective service workers (CSWs) are at high risk of post-traumatic stress disorder (PTSD) and other mental health problems. Prevalence rates and help-seeking behaviours are under-researched within this population. AIMS: To assess rates of PTSD and distress, and identify predictors of intention to seek help, among workers at an Australian corrective service agency. METHODS: A cross-sectional online survey was used to collect data on staff demographics, employment, PTSD symptoms and current distress. Participants received a tailored feedback report including referral to relevant mental health services (where applicable) and were asked to indicate their likelihood of seeking help. Prevalence data are reported. Binary logistic regression was used to examine relationships between participant characteristics and help-seeking for those with probable PTSD and/or high psychological distress. RESULTS: Participants (n=1001) were predominantly men (56.8%) with a mean age of 46.72 (SD=11.00). Over half (58.0%) were classified as probable PTSD cases, and one-third (33.0%) were experiencing high psychological distress. Around a third (34.3%) of participants with probable PTSD and/or elevated distress indicated they were likely to seek help. Older age and fewer years of service were associated with increased help-seeking intentions. CONCLUSIONS: CSWs were found to be experiencing probable PTSD at higher rates than reported in previous studies. Relatively few intended to seek help from mental health services, despite being provided with personalised screening and feedback along with access to specialised care. Future research should investigate the potential role of organisational support as a facilitator of help-seeking within this population.

The impact of age-related differences in emotion dysregulation on refugee mental health and social outcomes.

The refugee experience is typically characterized by exposure to numerous premigration traumatic events and postmigration stress in the resettlement environment. Refugees' experiences can lead to elevated rates of psychopathology, including posttraumatic stress disorder (PTSD) and depression. Emotion regulation is a key mechanism contributing to mental health outcomes among refugees. This study examined the impact of age on the association between emotion regulation and critical social outcomes relevant to refugee resettlement, such as social engagement and functional impairment. Participants were 1,081 Arabic-, Farsi-, Tamil- and English-speaking adult refugees. Premigration trauma exposure, postmigration stressors, PTSD symptoms, depressive symptoms, emotion regulation, social engagement, and functional impairment were measured. A series of hierarchical regression and Poisson regression analyses revealed emotion dysregulation as a significant predictor of functional impairment, ß = .36, p < .001, and social engagement, Exp B = 0.99, p = .002. A significant interaction between age and emotion dysregulation was associated with both PTSD, ß = .05, p = .048 and depressive symptoms, ß = .06, p = .010, suggesting a stronger positive association between emotion dysregulation and both PTSD and depressive symptom severity for older individuals. Postmigration stressor exposure, emotion dysregulation, and older age are important factors that may negatively impact social engagement and functional impairment in the resettlement environment. Additionally, higher levels of trauma exposure may negatively impact social engagement. These findings have implications for public health and social services in the context of resettled refugee communities.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.

Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.

A comparison of the functional connectome in mild traumatic brain injury and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) often co-occur in the context of threat to one's life. These conditions also have an overlapping symptomatology and include symptoms of anxiety, poor concentration and memory problems. A major challenge has been articulating the underlying neurobiology of these overlapping conditions. The primary aim of this study was to compare intrinsic functional connectivity between mTBI (without PTSD) and PTSD (without mTBI). The study included functional MRI data from 176 participants: 42 participants with mTBI, 67 with PTSD and a comparison group of 66 age and sex-matched healthy controls. We used network-based statistical analyses for connectome-wide comparisons of intrinsic functional connectivity between mTBI relative to PTSD and controls. Our results showed no connectivity differences between mTBI and PTSD groups. However, we did find that mTBI had significantly reduced connectivity relative to healthy controls within an extensive network of regions including default mode, executive control, visual and auditory networks. The mTBI group also displayed hyperconnectivity between dorsal and ventral attention networks and perceptual regions. The PTSD group also demonstrated abnormal connectivity within these networks relative to controls. Connectivity alterations were not associated with severity of PTSD or post-concussive symptoms in either clinical group. Taken together, the similar profiles of intrinsic connectivity alterations in these two conditions provide neural evidence that can explain, in part, the overlapping symptomatology between mTBI and PTSD.

The management of depression: the evidence speaks for itself.

Comparing the recommendations of two recently published national clinical practice guidelines for depression, this editorial highlights the concordance of advice concerning the selection and sequencing of therapies. Lifestyle and psychological interventions feature prominently and there is broad agreement regarding medication choice and optimisation strategies. The guidelines are therefore a useful resource.

Suicide among emergency service workers: a retrospective mortality study of national coronial data, 2001-2017.

BACKGROUND: Emergency service workers (ESW) are known to be at increased risk of mental disorders but population-level and longitudinal data regarding their risk of suicide are lacking. METHOD: Suicide data for 2001-2017 were extracted from the Australian National Coronial Information Service (NCIS) for two occupational groups: ESW (ambulance personnel, fire-fighters and emergency workers, police officers) and individuals employed in all other occupations. Age-standardised suicide rates were calculated and risk of suicide compared using negative binomial regression modelling. RESULTS: 13 800 suicide cases were identified among employed adults (20-69 years) over the study period. The age-standardised suicide rate across all ESW was 14.3 per 100 000 (95% CI 11.0-17.7) compared to 9.8 per 100 000 (95% CI 9.6-9.9) for other occupations. Significant occupational differences in the method of suicide were identified (p < 0.001). There was no evidence for increased risk of suicide among ESW compared to other occupations once age, gender and year of death were accounted for (RR = 0.99, 95% CI 0.84-1.17; p = 0.95). In contrast, there was a trend for ambulance personnel to be at elevated risk of suicide (RR = 1.41, 95% CI 1.00-2.00, p = 0.053). CONCLUSION: Whilst age-standardised suicide rates among ESW are higher than other occupations, emergency service work was not independently associated with an increased risk of suicide, with the exception of an observed trend in ambulance personnel. Despite an increased focus on ESW mental health and wellbeing over the last two decades, there was no evidence that rates of suicide among ESW are changing over time.

Mental health across the early years in the military.

BACKGROUND: The mental health impact of the initial years of military service is an under-researched area. This study is the first to explore mental health trajectories and associated predictors in military members across the first 3-4 years of their career to provide evidence to inform early interventions. METHODS: This prospective cohort study surveyed Australian Defence personnel (n = 5329) at four time-points across their early military career. Core outcomes were psychological distress (K10+) and posttraumatic stress symptoms [four-item PTSD Checklist (PCL-4)] with intra-individual, organizational and event-related trajectory predictors. Latent class growth analyses (LCGAs) identified subgroups within the sample that followed similar longitudinal trajectories for these outcomes, while conditional LCGAs examined the variables that influenced patterns of mental health. RESULTS: Three clear trajectories emerged for psychological distress: resilient (84.0%), worsening (9.6%) and recovery (6.5%). Four trajectories emerged for post-traumatic stress, including resilient (82.5%), recovery (9.6%), worsening (5.8%) and chronic subthreshold (2.3%) trajectories. Across both outcomes, prior trauma exposure alongside modifiable factors, such as maladaptive coping styles, and increased anger and sleep difficulties were associated with the worsening and chronic subthreshold trajectories, whilst members in the resilient trajectories were more likely to be male, report increased social support from family/friends and Australian Defence Force (ADF) sources, and use adaptive coping styles. CONCLUSIONS: The emergence of symptoms of mental health problems occurs early in the military lifecycle for a significant proportion of individuals. Modifiable factors associated with wellbeing identified in this study are ideal targets for intervention, and should be embedded and consolidated throughout the military career.

Effect of massed v. standard prolonged exposure therapy on PTSD in military personnel and veterans: a non-inferiority randomised controlled trial.

BACKGROUND: A short, effective therapy for posttraumatic stress disorder (PTSD) could decrease barriers to implementation and uptake, reduce dropout, and ameliorate distressing symptoms in military personnel and veterans. This non-inferiority RCT evaluated the efficacy of 2-week massed prolonged exposure (MPE) therapy compared to standard 10-week prolonged exposure (SPE), the current gold standard treatment, in reducing PTSD severity in both active serving and veterans in a real-world health service system. METHODS: This single-blinded multi-site non-inferiority RCT took place in 12 health clinics across Australia. The primary outcome was PTSD symptom severity measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks. 138 military personnel and veterans with PTSD were randomised. 71 participants were allocated to SPE, with 63 allocated to MPE. RESULTS: The intention-to-treat sample included 138 participants, data were analysed for 134 participants (88.1% male, M = 46 years). The difference between the mean MPE and SPE group PTSD scores from baseline to 12 weeks-post therapy was 0.94 [95% confidence interval (CI) -4.19 to +6.07]. The upper endpoint of the 95% CI was below +7, indicating MPE was non-inferior to SPE. Significant rates of loss of PTSD diagnosis were found for both groups (MPE 53.8%, SPE 54.1%). Dropout rates were 4.8% (MPE) and 16.9% (SPE). CONCLUSIONS: MPE was non-inferior to SPE in significantly reducing symptoms of PTSD. Significant reductions in symptom severity, low dropout rates, and loss of diagnosis indicate MPE is a feasible, accessible, and effective treatment. Findings demonstrate novel methods to deliver gold-standard treatments for PTSD should be routinely considered.

Massed v. standard prolonged exposure therapy for PTSD in military personnel and veterans: 12-month follow-up of a non-inferiority randomised controlled trial.

BACKGROUND: The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. METHODS: A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). RESULTS: Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. CONCLUSIONS: The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Significant age by childhood trauma interactions on grey matter volumes: A whole brain VBM analysis.

BACKGROUND: Childhood trauma is deleterious to long term brain development. The changes are variable, and depend on gender, age and the nature of the trauma. In this exploratory analysis, we investigated the effects of exposure to emotional trauma on grey matter (GM) volumes in adolescent females. METHODS: We explored GM volumes in non-clinical females aged 12-17 years who had been exposed to either higher (HET; N = 75) or minimal (MET; N = 127) emotional trauma. High-resolution T1-weighted structural images were analysed with an optimised FSL-VBM protocol. The General Linear Model was run on HET versus MET with continuous age as an interaction. Mean GM volumes were extracted from significant corrected age interaction statistical maps and scrutinised with SPSS®. RESULTS: We observed greater HET*age than MET*age interactions (corrected p-value = 0.0002), in 4 separate bilateral cortical regions associated with mood disorders. Scrutiny of these regions showed significant GM volume enlargements in the early adolescent HET group (p = 0.017) and reductions in the late adolescent HET group (p < 0.0001). Notably, there were no differences in middle adolescence (p > 0.05). LIMITATIONS: Causality cannot be inferred from this cross-sectional study and the onset of trauma cannot be determined using retrospective measures. CONCLUSIONS: Whilst GM volumes diminish from early adolescence onwards, our results show that HET impacts this brain development, perhaps first via unstable adaptative mechanisms, followed by maladaptive processes in late adolescence. This suggests that compromises of emotional and cognitive self-regulation in mood disorders may underpin the structural abnormalities observed across multiple brain regions in these teenage girls.

Same-day discharge robot-assisted laparoscopic prostatectomy: feasibility, safety and patient experience.

OBJECTIVES: To report a single centre's experience of the feasibility, safety and patient acceptability of same-day discharge robot-assisted laparoscopic prostatectomy (RALP). SUBJECTS/PATIENTS AND METHODS: Between June 2015 and December 2021, a total of 180 pre-selected consecutive patients underwent RALP with the intention to discharge on the same day as surgery. Cases were performed by two surgeons. An enhanced recovery after surgery (ERAS) programme was used. The feasibility of same-day discharge was analysed, along with the complication rate, oncological outcomes, and postoperative patient experience. RESULTS: Of 180 patients, 169 (93.8%) were successfully discharged on the same day as surgery. The median (range) age was 63 ( 44-74) years. The median (range) console time was 97 (61-256) min and blood loss was 200 (20-800) mL. The resection specimen pathology results were: pT2 69.4%, pT3a 24.4% and pT3b 6.5%. With regard to Gleason Grade Group (GGG), 25.9% had GGG 1, 65.7% had GGG 2-3 and 8.4% had GGG 4-5 disease. Positive surgical margins were present in 25 cases (14.7%), 18 (15.5%) of which occurred in pT2 cases, and seven (13.4%) in pT3 cases. There were no early (<90 days) biochemical relapses (defined as prostate-specific antigen level >0.2 ng/mL). The 30-day readmission rate was 3%. A total of 13 early (0-30 days) complications were observed, five of which were Clavien-Dindo grade ≥3, however, none of these would have been avoided had the patient remained in hospital on the first postoperative night. Of 121 consecutive patients, 107 (88%) returned a satisfaction questionnaire, and 92% of responders stated they preferred recovery at home, with 94% stating they felt ready to go home. CONCLUSION: Robot-assisted laparoscopic prostatectomy combined with an ERAS programme allows patients to be safely discharged home on the same day of their surgery. This is a feasible option, well-liked by patients, with morbidity and oncological outcomes similar to non-day-case or 23 h stay RALP.

Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Workplace mental health screening: a systematic review and meta-analysis.

Workplaces are an important location for population mental health interventions. Screening to detect employees at risk of or experiencing mental ill health is increasingly common. This systematic review and meta-analysis examined the efficacy of workplace mental health screening programmes on employee mental health, work outcomes, user satisfaction, positive mental health, quality of life, help-seeking and adverse effects. PubMed, PsycINFO, EMBASE, CENTRAL, Global Index Medicus, Global Health and SciELO were searched (database inception-10 November 2022) and results screened by two independent reviewers. Controlled trials evaluating screening of workers' mental health as related to their employment were included. Random effects meta-analysis was performed to calculate pooled effect sizes for each outcome of interest. Grading of Recommendations Assessment, Development and Evaluation was conducted to evaluate the certainty of findings. Of the 12 328 records screened, 11 were included. These reported 8 independent trials collectively assessing 2940 employees. Results indicated screening followed by advice or referral was ineffective in improving employee mental health symptoms (n=3; d=-0.07 (95% CI -0.29 to 0.15)). Screening followed by facilitated access to treatment interventions demonstrated a small improvement in mental health (n=4; d=-0.22 (95% CI -0.42 to -0.02)). Limited effects were observed for other outcomes. Certainty ranged from low to very low. The evidence supporting workplace mental health screening programmes is limited and available data suggest mental health screening alone does not improve worker mental health. Substantial variation in the implementation of screening was observed. Further research disentangling the independent effect of screening alongside the efficacy of other interventions to prevent mental ill health at work is required.