Effectiveness of a group psychological intervention to reduce psychosocial distress in adolescents in Pakistan: a single-blind, cluster randomised controlled trial.

BACKGROUND: Emotional problems in adolescents living in low-income and middle-income countries (LMICs) remain largely unaddressed; key reasons include a scarcity of trained mental health professionals and unavailability of evidence-based, scalable psychological interventions. We aimed to evaluate the effectiveness of a non-specialist-delivered, group psychological intervention to reduce psychosocial distress in school-going adolescents in Pakistan. METHODS: In a two-arm, single-blind, cluster randomised controlled trial, eligible public school clusters from a rural subdistrict of Gujar Khan, Rawalpindi, Pakistan, were randomised (1:1, stratified by sex) using permuted block randomisation into intervention (n=20) and wait-list control (n=20) groups. Adolescents aged 13-15 years who provided informed assent and caregivers' consent were screened for psychosocial distress using the youth-reported Pediatric Symptoms Checklist (PSC; total psychosocial distress scores from 0 to 70), and those scoring 28 or more and their caregivers were enrolled into the trial. Adolescents in the intervention group received seven weekly group sessions and their caregivers received three biweekly group sessions in school settings from trained non-specialists. The primary outcome was change from baseline in the total PSC scores at 3 months post-intervention. The trial was registered prospectively with the International Standard Randomised Controlled Trial Number registry, ISRCTN17755448. FINDINGS: From the 40 school clusters that were included, 282 adolescents in the intervention group and 284 adolescents in the wait-list control group were enrolled between Nov 2 and Nov 30, 2021. At 3 months, adolescents in the intervention group had significantly lower mean total score on the PSC compared with adolescents in the control group (mean difference in change from baseline 3·48 [95% CI 1·66-5·29], p=0·0002, effect size 0·38 [95% CI 0·18-0·57]; adjusted mean difference 3·26 (95% CI 1·46-5·06], p=0·0004, effect size 0·35 (0·16-0·55). No adverse events were reported in either group. INTERPRETATION: The group psychological intervention most likely represents a feasible and effective option for adolescents with psychosocial distress in school settings. FUNDING: UK Medical Research Council, Foreign Commonwealth and Development Office, Department of Health and Social Care. TRANSLATION: For the Urdu translation of the abstract see Supplementary Materials section.

Do aversive well-being comparisons mediate the effects of childhood adversity on anxiety and depression?

BACKGROUND: Childhood adversity (CA) is strongly associated with depression and anxiety in later life. Many adults with a history of CA may have internalized an insecure self-concept, which may contribute to negative evaluations of one's current well-being relative to different standards. Yet, there is lack of research on well-being comparisons in adults with a history of CA. OBJECTIVE: We examined aversive well-being comparisons (i.e., comparisons threatening the comparer's motives) in the context of CA and their predictive value in depression and anxiety beyond self-esteem, emotion regulation, and external control beliefs. Further, we investigated whether well-being comparison processes mediate the relationship between CA and depression and anxiety. PARTICIPANTS AND SETTING: We conducted a two-wave longitudinal study with 942 adult participants (mean age: 31.56 years, SD = 10.49, 18-75 years). METHODS: Participants completed measures of CA, aversive well-being comparisons (social, temporal, counterfactual, and criteria-based comparisons), self-esteem, emotion regulation, and locus of control at two time points, three months apart. RESULTS: CA was significantly linked to more frequent aversive well-being comparisons. These comparisons were associated with greater discrepancies relative to the comparison standard and a more negative affective impact, ultimately contributing to higher levels of subsequent anxiety and depression symptoms. Comparison frequency emerged as key mediator, highlighting potential pathways through which CA affects adult mental health. These associations emerged despite controlling for established variables in this context, namely self-esteem, emotion regulation, and external locus of control. CONCLUSION: Our findings underscore the unique importance of aversive well-being comparisons in individuals with a history of CA.

Moral injury appraisals and complex PTSD in refugees: A longitudinal study.

OBJECTIVE: Refugees show elevated rates of complex posttraumatic stress disorder (CPTSD). However, relatively little is known regarding the psychological mechanisms that underlie the association between exposure to potentially traumatic events (PTEs) and CPTSD following exposure to war, persecution and displacement. In this study, we investigated the potential mediating role of moral injury appraisals (cognitive appraisals regarding the experience and consequences of morally transgressive events) in the association between PTE exposure, posttraumatic stress disorder (PTSD), and disturbances in self-organization (DSO) symptoms. METHOD: Participants were 889 refugees from Arabic-, Farsi-, Tamil-, and English-speaking backgrounds who completed an online survey in their own language at two time points 12 months apart. We assessed PTE exposure, moral injury-other appraisals (appraising moral transgressions as enacted by others), moral injury-self appraisals (appraising moral transgressions as enacted by the self), PTSD symptoms, and DSO symptoms. RESULTS: Longitudinal structural equation modeling indicated that moral injury-other appraisals mediated the association between PTE exposure and both PTSD and DSO symptoms. In contrast, moral injury-self appraisals only mediated the association between PTE exposure and DSO symptoms. CONCLUSIONS: Findings highlight the role of moral injury appraisals in exacerbating traditional PTSD symptoms, as well as the broader symptoms characteristic of CPTSD. Further, results indicate that specific types of moral injury appraisals (relating to one's own and others' perceived moral transgressions) may lead to differential psychological reactions, raising important implications for clinical practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sympathetic Duet: Simultaneous Stellate Ganglion Block and Thoracic Epidural Analgesia in the Successful Termination of Ventricular Storm.

This article discusses the management of ventricular storm (VS), a condition characterized by recurrent episodes of sustained ventricular tachycardia or fibrillation, which poses a significant risk of mortality. Prompt intervention is crucial, yet surgical options are often limited due to the patient's unstable condition. This case report presents a 47-year-old female who experienced VS during a planned surgical procedure. Despite initial stabilization, she continued to experience life-threatening arrhythmias, prompting the implementation of simultaneous stellate ganglion block (SGB) and thoracic epidural analgesia (TEA) catheters. This combined approach successfully controlled the arrhythmias, allowing for subsequent surgical interventions. The article emphasizes the potential of SGB and TEA as a bridge to definitive therapies for refractory VS, highlighting the need for further research to solidify their role in clinical practice.

Statistical analysis plan for the TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation of potentially clinically significant prostate cancer) multicentre randomised controlled trial.

BACKGROUND: The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures in terms of detection of clinically significant prostate cancer (PCa). This article describes the statistical analysis plan (SAP) for the TRANSLATE randomised controlled trial (RCT). METHODS/DESIGN: TRANSLATE is a parallel, superiority, multicentre RCT. Biopsy-naïve men aged ≥ 18 years requiring a prostate biopsy for suspicion of possible PCa are randomised (computer-generated 1:1 allocation ratio) to one of two biopsy procedures: transrectal (TRUS) or local anaesthetic transperineal (LATP) biopsy. The primary outcome is the difference in detection rates of clinically significant PCa (defined as Gleason Grade Group ≥ 2, i.e. any Gleason pattern ≥ 4 disease) between the two biopsy procedures. Secondary outcome measures are th eProBE questionnaire (Perception Part and General Symptoms) and International Index of Erectile Function (IIEF, Domain A) scores, International Prostate Symptom Score (IPSS) values, EQ-5D-5L scores, resource use, infection rates, complications, and serious adverse events. We describe in detail the sample size calculation, statistical models used for the analysis, handling of missing data, and planned sensitivity and subgroup analyses. This SAP was pre-specified, written and submitted without prior knowledge of the trial results. DISCUSSION: Publication of the TRANSLATE trial SAP aims to increase the transparency of the data analysis and reduce the risk of outcome reporting bias. Any deviations from the current SAP will be described and justified in the final study report and results publication. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN98159689, registered on 28 January 2021 and registered on the ClinicalTrials.gov (NCT05179694) trials registry.

A systematic review and meta-analysis of predictors of response to trauma-focused psychotherapy for posttraumatic stress disorder.

Although trauma-focused psychotherapy (T-F psychotherapy) is the treatment of choice for posttraumatic stress disorder (PTSD), up to one half of patients do not respond to this treatment. Attempts to improve response to T-F psychotherapy have focused on augmenting fear extinction-based factors. Here, a systematic and meta-analytic review of predictors of T-F psychotherapy outcome was conducted with the goal of using an aggregate data-driven approach to elucidate baseline factors associated with treatment outcome. There were 114 studies that met inclusion criteria (N = 61, 970; Mage = 40.1 years; 40.1% female). There were 237 effect sizes across 24 meta-analytic categories. Poorer treatment response is associated with lower pretreatment levels of activation of fear-related brain regions, psychophysiological reactivity to fear provocation, trauma-related cognitions, anger, depression, high-risk alleles of genes linked to fear, lower levels of executive control, and social support. A range of other factors also predicted poorer responses including being male, non-Caucasian, older in age, early trauma occurrence, more trauma experience, history of combat trauma, as well as comorbid sleep, pain, poor quality life, and alcohol abuse difficulties. This review provides one potential explanation for the limited success of T-F psychotherapy augmentation strategies that have focused only on fear circuity mechanisms at the exclusion of other factors. Here, poor response relating to predictors of early trauma onset and comorbidity are consistent with clinical presentations of complex PTSD, which may suggest T-F psychotherapy is less effective for this condition. This collective evidence suggests that clinicians should consider a tailored approach that targets potential barriers to successful treatment response. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cultural differences in appraisals of control and posttraumatic stress disorder symptoms.

Background: Appraisals are central to posttraumatic stress disorder (PTSD). Yet, few studies have examined how culture influences the associations between different types of trauma-related appraisals and PTSD symptoms.Objective: This study investigated cultural influences on appraisals of control and their associations with PTSD symptoms.Method: European Australian (n = 140, Mage = 35.80, SD = 12.44; 21 men, 97 women, 20 gender diverse/prefer not to report) and Chinese Australian (n = 129, Mage = 30.16, SD = 8.93, 21 men, 97 women, 20 gender diverse/prefer not to report) trauma survivors completed measures of appraisals, cultural values, and PTSD symptoms.Results: Findings showed that the Chinese Australian group was associated with greater Chinese cultural beliefs about adversity (i.e. emphasizing the value of adversity and people's ability to overcome adversity) and fewer fatalism appraisals (i.e. appraising one's destiny as externally determined), which in turn were atemporally associated with fewer PTSD symptoms; these atemporal indirect associations were moderated by self-construal and holistic thinking. The Chinese Australian group also reported fewer secondary control appraisals (i.e. attempts to change aspects of the self and accept current circumstances), which were atemporally associated with greater PTSD symptoms. In contrast, the European Australian group was associated with fewer primary control appraisals (i.e. perceived ability to personally change or control a situation), which were atemporally associated with greater PTSD symptoms.Conclusion: These findings highlight the importance of considering the influence of culture on appraisals in PTSD. However, it must be noted that causal relationships cannot be inferred from cross-sectional mediation analyses and thus, future longitudinal research is needed.

Chinese Australian trauma survivors were associated with greater reporting of Chinese cultural beliefs about adversity and fewer fatalism appraisals, which were associated with fewer PTSD symptoms. These associations were moderated by a trauma survivor's self-construal and level of holistic thinking.Chinese Australian trauma survivors reported fewer secondary control appraisals, which were associated with greater PTSD symptoms.European Australian trauma survivors were associated with fewer primary control appraisals, which were associated with greater PTSD symptoms.

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 .

Adjuvant COX inhibition augments STING signaling and cytolytic T cell infiltration in irradiated 4T1 tumors.

Immune therapy is the new frontier of cancer treatment. Therapeutic radiation is a known inducer of immune response and can be limited by immunosuppressive mediators including cyclooxygenase-2 (COX2) that is highly expressed in aggressive triple negative breast cancer (TNBC). A clinical cohort of TNBC tumors revealed poor radiation therapeutic efficacy in tumors expressing high COX2. Herein, we show that radiation combined with adjuvant NSAID (indomethacin) treatment provides a powerful combination to reduce both primary tumor growth and lung metastasis in aggressive 4T1 TNBC tumors, which occurs in part through increased antitumor immune response. Spatial immunological changes including augmented lymphoid infiltration into the tumor epithelium and locally increased cGAS/STING1 and type I IFN gene expression were observed in radiation-indomethacin-treated 4T1 tumors. Thus, radiation and adjuvant NSAID treatment shifts "immune desert phenotypes" toward antitumor M1/TH1 immune mediators in these immunologically challenging tumors. Importantly, radiation-indomethacin combination treatment improved local control of the primary lesion, reduced metastatic burden, and increased median survival when compared with radiation treatment alone. These results show that clinically available NSAIDs can improve radiation therapeutic efficacy through increased antitumor immune response and augmented local generation of cGAS/STING1 and type I IFNs.

Self-construal modulates default mode network connectivity in refugees with PTSD.

BACKGROUND: While self-construal and posttraumatic stress disorder (PTSD) are independently associated with altered self-referential processes and underlying default mode network (DMN) functioning, no study has examined how self-construal affects DMN connectivity in PTSD. METHODS: A final sample of 93 refugee participants (48 with DSM-5 PTSD or sub-syndromal PTSD and 45 matched trauma-exposed controls) completed a 5-minute resting state fMRI scan to enable the observation of connectivity in the DMN and other core networks. A self-construal index was calculated by substracting scores on the collectivistic and individualistic sub-scales of the Self Construal Scale. RESULTS: Independent components analysis identified 9 active networks-of-interest, and functional network connectivity was determined. A significant interaction effect between PTSD and self-construal index was observed in the anterior ventromedial DMN, with spatial maps localizing this to the left ventromedial prefrontal cortex (vmPFC), extending to the ventral anterior cingulate cortex. This effect revealed that connectivity in the vMPFC showed greater reductions in those with PTSD with higher levels of collectivistic self-construal. LIMITATIONS: This is an observational study and causality cannot be assumed. The specialized sample of refugees means that the findings may not generalize to other trauma-exposed populations. CONCLUSIONS: Such a finding indicates that self-construal may shape the core neural architecture of PTSD, given that functional disruptions to the vmPFC underpin the core mechanisms of extinction learning, emotion dysregulation and self-referential processing in PTSD. Results have important implications for understanding the universality of neural disturbances in PTSD, and suggest that self-construal could be an important consideration in the assessment and treatment of post-traumatic stress reactions.

The course of symptoms over time in people with posttraumatic stress disorder.

OBJECTIVE: There is inadequate evidence regarding the symptom profile of people who have posttraumatic stress disorder (PTSD) over time. The goal of this study was to determine the consistency of symptoms in people with PTSD over successive assessments. METHOD: The sample comprised military personnel who participated in the Army Study to Assess Risk and Resilience in Servicemembers. Participants completed the PTSD Checklist, and this sample included those who completed two assessments. RESULTS: There were 1,164 participants with two consecutive PTSD diagnoses. Only 212 (18.2%) of participants reported the same number of symptoms over both timepoints. Intrusive memories, distress to reminders, avoidance, detachment, and sleep problems were among the most reported symptoms at the second assessment not reported initially. CONCLUSIONS: The observed pattern of findings indicate that although PTSD diagnoses often remain consistent over time, the symptoms that comprise this diagnosis can fluctuate. Clinicians should be sensitive to the changing symptoms that PTSD patients can display over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A pilot study of the role of the BDNF Val66Met polymorphism in response to exercise-augmented exposure therapy for posttraumatic stress disorder.

Brain-Derived Neurotrophic Factor (BDNF) is implicated in extinction learning, which is a primary mechanism of exposure therapy for posttraumatic stress disorder (PTSD). Brief aerobic exercise has been shown to promote BDNF release and augment extinction learning. On the premise that the Val allele of the BDNF Val66Met polymorphism facilitates greater release of BDNF, this study examined the extent to which the Val allele of the BDNF polymorphism predicted treatment response in PTSD patients who underwent exposure therapy combined with aerobic exercise or passive stretching. PTSD patients (N = 85) provided saliva samples in order to extract genomic DNA to identify Val/Val and Met carriers of the BDNF Val66Met genotype, and were assessed for PTSD severity prior to and following a 9-week course of exposure therapy combined with aerobic exercise or stretching. The sample comprised 52 Val/Val carriers and 33 Met carriers. Patients with the BDNF high-expression Val allele display greater reduction of PTSD symptoms at posttreatment than Met carriers. Hierarchical regression analysis indicated that greater PTSD reduction was specifically observed in Val/Val carriers who received exposure therapy in combination with the aerobic exercise. This finding accords with animal and human evidence that the BDNF Val allele promotes greater extinction learning, and that these individuals may benefit more from exercise-augmented extinction. Although preliminary, this result represents a possible avenue for augmented exposure therapy in patients with the BDNF Val allele.

Structural covariance, topological organization, and volumetric features of amygdala subnuclei in posttraumatic stress disorder.

The amygdala is divided into functional subnuclei which have been challenging to investigate due to functional magnetic resonance imaging (MRI) limitations in mapping small neural structures. Hence their role in the neurobiology of posttraumatic stress disorder (PTSD) remains poorly understood. Examination of covariance of structural MRI measures could be an alternate approach to circumvent this issue. T1-weighted anatomical scans from a 3 T scanner from non-trauma-exposed controls (NEC; n = 71, 75 % female) and PTSD participants (n = 67, 69 % female) were parcellated into 105 brain regions. Pearson's r partial correlations were computed for three and nine bilateral amygdala subnuclei and every other brain region, corrected for age, sex, and total brain volume. Pairwise correlation comparisons were performed to examine subnuclei covariance profiles between-groups. Graph theory was employed to investigate subnuclei network topology. Volumetric measures were compared to investigate structural changes. We found differences between amygdala subnuclei in covariance with the hippocampus for both groups, and additionally with temporal brain regions for the PTSD group. Network topology demonstrated the importance of the right basal nucleus in facilitating network communication only in PTSD. There were no between-group differences for any of the three structural metrics. These findings are in line with previous work that has failed to find structural differences for amygdala subnuclei between PTSD and controls. However, differences between amygdala subnuclei covariance profiles observed in our study highlight the need to investigate amygdala subnuclei functional connectivity in PTSD using higher field strength fMRI for better spatial resolution.

Dimensionality of the Swahili version of the General Health Questionnaire (GHQ-12) in a Kenyan population: A confirmatory factor analysis.

The current study evaluated the Kiswahili version of General Health Questionnaire (GHQ-12) in a Kenyan context comprising of women exposed to gender-based violence. Participants were randomly drawn from community sampling using household screening methods in peri-urban areas in Nairobi. A total of 1,394 participants with varying levels of literacy (years of education: mean [M] = 9.42; standard deviation [SD] = 3.73) and aged between 18 and 89 years were recruited for the study. The observed factor structure of the GHQ-12 was evaluated using six most tested models querying the dimensionality of the instrument insofar as the impacts of positive and negative wording effects in driving multidimensionality. Results from the confirmatory factor analysis supported a bifactor model, consisting of a general distress factor and two separate factors representing common variance due to the positive and negative wording of items. Overall, the findings support the use of the Kiswahili version of the GHQ-12 as a unidimensional construct with method-specific variance owing to wording effects. Importantly, GHQ-12 responses from a sample of Kenyan women with relatively low levels of literacy are congruent with the factor structure observed in other cross-cultural settings in low- and-middle-income countries.

Validation of Arabic versions of the child psychosocial distress screener and pediatric symptom checklist for young adolescents living in vulnerable communities in Lebanon.

BACKGROUND: In humanitarian settings, brief screening instruments for child psychological distress have potential to assist in assessing prevalence, monitoring outcomes, and identifying children and adolescents in most need of scarce resources, given few mental health professionals for diagnostic services. Yet, there are few validated screening tools available, particularly in Arabic. METHODS: We translated and adapted the Child Psychosocial Distress Screener (CPDS) and the Pediatric Symptom Checklist (PSC) and conducted a validation study with 85 adolescents (aged 10-15) in Lebanon. We assessed internal consistency; test-retest reliability; convergent validity between adolescent- and caregiver-report and between the two measures; ability to distinguish between clinical and non-clinical samples; and concurrent validity against psychiatrist interview using the Kiddie Schedule for Affective Disorders and Schizophrenia. RESULTS: The translated and adapted child-reported PSC-17 and PSC-35, and caregiver-reported PSC-35 all showed adequate internal consistency and test-retest reliability and high concurrent validity with psychiatrist interview and were able to distinguish between clinical and non-clinical samples. However, the caregiver-reported PSC-17 did not demonstrate adequate performance in this setting. Child-reported versions of the PSC outperformed caregiver-reported versions and the 35-item PSC scales showed stronger performance than 17-item scales. The CPDS showed adequate convergent validity with the PSC, ability to distinguish between clinical and non-clinical samples, and concurrent validity with psychiatrist interview. Internal consistency was low for the CPDS, likely due to the nature of the brief risk-screening tool. There were discrepancies between caregiver and child-reports, worthy of future investigation. For indication of any diagnosis requiring treatment, we recommend cut-offs of 5 for CPDS, 12 for child-reported PSC-17, 21 for child-reported PSC-35, and 26 for caregiver-reported PSC-35. CONCLUSIONS: The Arabic PSC and CPDS are reliable and valid instruments for use as primary screening tools in Lebanon. Further research is needed to understand discrepancies between adolescent and caregiver reports, and optimal methods of using multiple informants.

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.

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?

The future of psychological treatments: The Marburg Declaration.

Although psychological treatments are broadly recognized as evidence-based interventions for various mental disorders, challenges remain. For example, a substantial proportion of patients receiving such treatments do not fully recover, and many obstacles hinder the dissemination, implementation, and training of psychological treatments. These problems require those in our field to rethink some of our basic models of mental disorders and their treatments, and question how research and practice in clinical psychology should progress. To answer these questions, a group of experts of clinical psychology convened at a Think-Tank in Marburg, Germany, in August 2022 to review the evidence and analyze barriers for current and future developments. After this event, an overview of the current state-of-the-art was drafted and suggestions for improvements and specific recommendations for research and practice were integrated. Recommendations arising from our meeting cover further improving psychological interventions through translational approaches, improving clinical research methodology, bridging the gap between more nomothetic (group-oriented) studies and idiographic (person-centered) decisions, using network approaches in addition to selecting single mechanisms to embrace the complexity of clinical reality, making use of scalable digital options for assessments and interventions, improving the training and education of future psychotherapists, and accepting the societal responsibilities that clinical psychology has in improving national and global health care. The objective of the Marburg Declaration is to stimulate a significant change regarding our understanding of mental disorders and their treatments, with the aim to trigger a new era of evidence-based psychological interventions.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Cognitive Behavior Therapy vs Mindfulness in Treatment of Prolonged Grief Disorder: A Randomized Clinical Trial.

Importance: Although grief-focused cognitive behavior therapies are the most empirically supported treatment for prolonged grief disorder, many people find this treatment difficult. A viable alternative for treatment is mindfulness-based cognitive therapy. Objective: To examine the relative efficacies of grief-focused cognitive behavior therapy and mindfulness-based cognitive therapy to reduce prolonged grief disorder severity. Design, Setting, and Participants: A single-blind, parallel, randomized clinical trial was conducted among adults aged 18 to 70 years with prolonged grief disorder, as defined in the International Classification of Diseases, 11th Revision, and assessed by clinical interview based on the Prolonged Grief-13 (PG-13) scale. Those with severe suicidal risk, presence of psychosis, or substance dependence were excluded. Between November 2012 and November 2022, eligible participants were randomized 1:1 to eleven 90-minute sessions of grief-focused cognitive behavior therapy or mindfulness-based cognitive therapy at a traumatic stress clinic in Sydney, Australia, with follow-up through 6 months. Interventions: Both groups received once-weekly 90-minute individual sessions for 11 weeks. Grief-focused cognitive behavior therapy comprised 5 sessions of recalling memories of the deceased, plus cognitive restructuring and planning future social and positive activities. Mindfulness-based cognitive therapy comprised mindfulness exercises adapted to tolerate grief-related distress. Main Outcomes and Measures: The primary outcome was change in prolonged grief disorder severity measured by the PG-13 scale assessed at baseline, 1 week posttreatment, and 6 months after treatment (primary outcome time point), as well as secondary outcome measures of depression, anxiety, grief-related cognition, and quality of life. Results: The trial included 100 participants (mean [SD] age, 47.3 [13.4] years; 87 [87.0%] female), 50 in the grief-focused cognitive behavior therapy condition and 50 in the mindfulness-based cognitive therapy condition. Linear mixed models indicated that at the 6-month assessment, participants in the grief-focused cognitive behavior therapy group showed greater reduction in PG-13 scale score relative to those in the mindfulness-based cognitive therapy group (mean difference, 7.1; 95% CI, 1.6-12.5; P = .01), with a large between-group effect size (0.8; 95% CI, 0.2-1.3). Participants in the grief-focused cognitive behavior therapy group also demonstrated greater reductions in depression as measured on the Beck Depression Inventory than those in the mindfulness-based cognitive therapy group (mean difference, 6.6; 95% CI, 0.5-12.9; P = .04) and grief-related cognition (mean difference, 14.4; 95% CI, 2.8-25.9; P = .02). There were no other significant differences between treatment groups and no reported adverse events. Conclusions and Relevance: In this study, grief-focused cognitive behavior therapy conferred more benefit for core prolonged grief disorder symptoms and associated problems 6 months after treatment than mindfulness-based cognitive therapy. Although both treatments may be considered for prolonged grief disorder, grief-focused cognitive behavior therapy might be the more effective choice, taking all factors into consideration. Trial Registration: anzctr.org.au Identifier: ACTRN12612000307808.