A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary.

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high-medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs - 80% had high-medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high-medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A qualitative study of patients with Cancer of Unknown Primary: Perceptions of communication, understanding of diagnosis and genomic testing, and information needs.

OBJECTIVE: Patients with Cancer of Unknown Primary (CUP) commonly report poor understanding of their illness and high levels of psychological distress. Despite the potential benefits to CUP patients, there is a paucity of research exploring the reasons behind poor understanding of a CUP diagnosis. The aim of this study was to understand patients' experiences of communication with doctors, their understanding of diagnosis and the role of genomic testing, as well as their information needs. METHODS: Semi-structured interviews explored CUP patients' perceptions of communication with their doctors, understanding of their illness, and their needs regarding medical information. Qualitative inductive thematic analysis of transcribed audio-recordings was employed. SETTING/PARTICIPANTS: Nineteen patients were recruited from within a prospective cohort study involving routine genomic testing of CUP patients. RESULTS: CUP patients had varied perceptions of communication with doctors as well as different levels of need, readiness, and capacity for information. Some patients felt well understood and supported by their doctors while others did not. Many patients reported feeling overwhelmed and shocked when receiving their cancer diagnosis and emphasized the importance of family support in receiving and understanding medical information. While patients understood the implications of genomic testing for treatment and diagnosis, few had a detailed understanding of genomic testing. CONCLUSIONS: Patients' experience of communication and understanding of CUP could be potentially improved by clinicians' assessment of the communication style preferred by each patient and their family and the development of online resources to meet their evolving information needs.

Suicidal ideation in men during COVID-19: an examination of protective factors.

BACKGROUND: Men account for three-quarters of all suicide deaths in many Western nations including Australia. Whilst extensive research has examined risk factors for suicidal ideation and behaviour in men, protective factors remain underexplored, particularly social support, resilience and coping behaviours. Such factors are important to examine particularly in the context of COVID-19, where enforced isolation (among other negative lifestyle effects) has created widespread risk for the development of suicidal ideation. This mixed-methods study aimed to examine associations of various protective factors with suicidal ideation in men, using data from an online survey conducted during the COVID-19 pandemic. In addition, we aimed to qualitatively investigate men's self-reported protective strategies when experiencing suicidal thoughts and behaviour. METHODS: A convenience sample of 700 men (age M = 50.3 years; SD = 15.2 years) responded to an online survey including quantitative measures of suicidal ideation, planning and attempt, alongside employment and relationship status, coping, social support, resilience, and a qualitative free-text item gauging men's self-reported protective strategies. Multinomial logistic regression was applied to compare odds of sub-categories of suicide risk (ideation; planning) according to protective factors. Qualitative responses were analysed via thematic analysis. RESULTS: Men in a relationship, and those lower in emotion-focused and avoidant coping reported lower odds of suicidal ideation. Maintaining employment throughout the pandemic was protective against suicidal ideation and planning; as was greater perceived social support from friends. Greater self-reported resilience was protective against suicidal ideation and planning. Qualitative analyses led to the development of two themes: coping and connecting, reflecting men's intra- and interpersonal management strategies; and sustaining selflessness, where men's imaginings of the collateral damage of their suicidal behaviour was protective against action on suicidal thoughts or plans. CONCLUSIONS: Findings of this study speak to the nuanced roles of interpersonal connections, resilience and coping behaviours in protecting against suicidal ideation and planning in men. In addition, qualitative insights further cement men's identification with familial protector and/or provider roles as protective against suicidal action.

Young men and anxiety: Resisting, reckoning and responding.

Anxiety is the most prevalent mental disorder experienced by young men, and when untreated, is predictive of co-morbid mental health challenges and suicide. Despite the rising prevalence, there is a conspicuous absence of qualitative research to distil and theorise young men's anxiety. Twenty-five young Australian men (15-25 years), who had been diagnosed with an anxiety disorder or self-reported anxiety symptoms, took part in individual semi-structured interviews. Interviews were transcribed verbatim and analysed using a constructivist grounded theory approach. A three-process grounded theory (Resisting-Reckoning-Responding; Triple R Anxiety Model) depicted young men's experiences of anxiety, gilded and guided by their masculine socialisation. Initially, young men noticed somatic symptoms (i.e., headaches, nausea and myalgia) but did not connect these symptoms to anxiety. Avoiding anxiety (e.g., denying, distracting) proved unhelpful in the longer term and as symptoms diffused, a subsequent process of reckoning anxiety (i.e., meaning making) ensued. As young men gained insight to the life limiting bounds of their anxiety, some were prompted towards actions of acceptance, seeking help proactively and employing strength-based adaptive coping strategies. This theoretical conceptualisation of young men's anxiety has the capacity to enhance identification and treatment efforts, improving young men's mental health outcomes across the lifespan.

Psychological distress, understanding of cancer and illness uncertainty in patients with Cancer of Unknown Primary.

OBJECTIVE: Patients diagnosed with Cancer of Unknown Primary (CUP) experience high levels of psychological distress and report poor understanding of their cancer. We aimed to investigate: (1) if CUP patients with poorer understanding of their cancer diagnosis and testing experience more symptoms of psychological distress than those with better understanding; (2) if the relationship between patients' understanding of their cancer and psychological distress is mediated by illness uncertainty; and (3) explore whether patients' degree of understanding of their cancer can be predicted by clinical and socio-demographic factors. METHODS: 209 CUP patients completed a questionnaire measuring anxiety, depression, illness uncertainty, fatigue, pain, sleep and understanding of their cancer. Using an apriori theoretical framework, we employed structural equation modelling to investigate predictors of patient's understanding of their cancer and psychological distress and the relationships between understanding, illness uncertainty and distress. RESULTS: The structural equation model displayed good fit indices and supported the hypothesised relationship of patient's understanding of their cancer and the extent of psychological distress, which was mediated via illness uncertainty. Physical symptoms were positively associated with psychological distress and illness uncertainty. Younger age was predictive of lower patient's understanding of their cancer and higher levels of psychological distress. CONCLUSIONS: Patients with CUP, particularly those who are younger and experiencing more physical symptoms, report higher levels of psychological distress and may require additional mental health support. Our findings highlight a need to improve CUP patient's understanding about their illness, which could help reduce their illness uncertainty and alleviate psychological distress.

Uncertainty and the unmet informational needs of patients with cancer of unknown primary (CUP): a cross-sectional multi-site study.

OBJECTIVE: This study aimed to determine the healthcare experiences, quality of life, and psychosocial needs of patients with cancer of unknown primary (CUP) early after diagnosis; comparing their experiences to patients with advanced cancer of a known primary (non-CUP control patients) and published general population reference data where available. METHODS: This study was a cross-sectional, multi-site study comparing CUP patients (n = 139) compared to non-CUP controls (n = 45). Demographic, clinical information and patient-reported outcome questionnaire data were collected at baseline. RESULTS: Differences in healthcare experienced were found between CUP and non-CUP controls with CUP patients reporting higher scores for unmet medical communication/information needs compared with non-CUP control patients (p = 0.013) as well as greater uncertainty in illness (p = 0.042). Whilst no differences were found between CUP and non-CUP controls on the EORTC and PROMIS measures, of those that 'received written information about your cancer…' and asked '…how useful was it?' fewer CUP patients reported finding the information useful 40% vs 61%, and more were likely to not have received written information at all 59% vs 32%; (p = 0.002). Additionally, of those that found information about their cancer online, fewer patients with CUP reported finding it useful 32% vs 48% control patients (p = 0.005). CONCLUSIONS: CUP patients have unmet medical communication/information needs and greater uncertainty in illness but do not differ in health-related quality of life domains compared to patients with advanced cancer of a known primary.

Australian men's initial pathways into mental health services.

ISSUE ADDRESSED: Many men are challenged by barriers to mental health help-seeking and engagement. For men who do access care, their pathways to engaging services can offer important insights to what might constitute gender-specific care. METHODS: Data were drawn from an online cross-sectional survey of N = 2009 Australian men (aged 16-85; M = 43.5) reflecting on their initial pathways to mental health services, including their reasons for help-seeking, how they first located a therapist and the source of any initial recommendation for engaging with services. Respondents were recruited with targeted advertisements via Movember's Facebook page. RESULTS: A relatively even age distribution was observed, with most respondents residing in metropolitan areas (60.4%), a majority employed full time (47.7%), and 25.7% identifying as gay or bisexual. Participants tended to be self-motivated to seek help, with referrals by general practitioners to specialist mental health services. The most common underpinning precipitant for seeking help was anxiety, particularly for younger men, whereas older men tended to have sought help more commonly for familial, relationship or work-related factors. Older men were also more likely to report self-motivated help-seeking, whereas younger men more commonly sought help on the recommendation of a family member. CONCLUSIONS: There are varied pathways for men's initial mental health help-seeking journeys that require an ongoing examination to ensure health promotion efforts are appropriately tailored and responding to men's needs. SO WHAT: As more men access mental health services, having a nuanced understanding of their likely pathways to care can inform the help-seeking efforts of other men as well as guide improved services and systems to reduce barriers.

The Mental Health of Elite-Level Coaches: A Systematic Scoping Review.

BACKGROUND: Elite-level coaches are exposed to multiple performance, organisational and personal stressors which may contribute to reduced mental health and wellbeing. This systematic scoping review examined the current body of evidence to explore what is known about the mental health of elite-level coaches (i.e. wellbeing and mental ill-health), the risk and protective factors that influence coach mental health, and the relationship between mental health and coaching effectiveness. METHODS: The review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search was undertaken and updated in September 2022 using six electronic databases. RESULTS: 12,376 studies were identified and screened, with 42 studies satisfying the inclusion criteria. Despite the paucity of high-quality research, findings indicated that 40% of the included studies examined themes connected to wellbeing, with 76% assessing the nature or prevalence of mental ill-health in elite-level coaches. Among studies exploring mental ill-health, coach burnout was the primary focus, while scant research examined symptoms associated with clinical disorders (e.g. anxiety and depression). Overall, psychological outcomes for elite-level coaches were shaped by risk and protective factors operating at the individual, interpersonal, organisational and societal level. Preliminary evidence was also found to suggest that poor mental health may contribute to reduced coaching effectiveness. It is proposed that coaching effectiveness could therefore be employed as a 'hook' to engage elite-level coaches in greater consideration of their mental health needs. CONCLUSION: Alongside the development of methodologically robust research, there is a need to examine dynamic individual (e.g. psychological skills), interpersonal (e.g. strong social supports) and organisational (e.g. workload) factors that aim to preserve the mental health and optimise the efficacy of elite-level coaches.

Approaches to Engaging Men During Primary Healthcare Encounters: A scoping review.

Gender-responsive healthcare is critical to advancing men's health given that masculinities intersect with other social determinants to impact help-seeking, engagement with primary healthcare, and patient outcomes. A scoping review was undertaken with the aim to synthesize gender-responsive approaches used by healthcare providers (HCPs) to engage men with primary healthcare. MEDLINE, PubMed, CINAHL, and PsycINFO databases were searched for articles published between 2000 and February 2024. Titles and abstracts for 15,659 citations were reviewed, and 97 articles met the inclusion criteria. Data were extracted and analyzed thematically. Thirty-three approaches were synthesized from across counseling/psychology, general practice, social work, nursing, psychiatry, pharmacy, and unspecified primary healthcare settings. These were organized into three interrelated themes: (a) tailoring communication to reach men; (b) purposefully structuring treatment to meet men's health needs, and (c) centering the therapeutic alliance to retain men in care. Strength-based and asset-building approaches focused on reading and responding to a diversity of masculinities was reinforced across the three findings. While these approaches are recommended for the judicious integration into health practitioner education and practice, this review highlighted that the evidence remains underdeveloped, particularly for men who experience health inequities. Critical priorities for further research include intersectional considerations and operationalizing gender-responsive healthcare approaches for men and its outcomes, particularly at first point-of-contact encounters.

"Hey Amir, How Are You REALLY Doing?": Participant Perspectives of a Peer-Based Suicide Prevention Campaign for Men.

Suicide is a major public health concern and leading cause of death among men in Canada. This study reports the feasibility and acceptability of Buddy Up, a peer-based suicide prevention campaign for men. A mixed-methods approach was used to analyze respondent survey questionnaires (n = 48) and individual participant interviews (n = 19) collected from campaign users. Survey respondents reported that they enjoyed their involvement in the campaign (92%), were more confident to talk with men about mental health and suicide (95%), and would recommend Buddy Up to others (95%). Qualitative interviews were thematically analyzed to develop three inductively derived themes: (a) Engaging men with relatable masculine content and design: "Buddy Up really spoke to them in their language," highlighting the importance of understanding and working with gendered practices and motivations to legitimize and motivate involvement in suicide prevention; (b) Leveraging campaign participation to initiate conversations and promote mental health: "It gives men language and license to start asking questions," revealing ways in which participants utilized Buddy Up to negotiate and norm checking-in to promote men's mental health; and (c) Driving new masculine cultures: "We start every meeting with a mental health moment," identifying how participants fostered healthy milieus for disclosing mental health challenges with teamwork and preventive action under the banner of Buddy Up. The study findings support the feasibility of Buddy Up and highlight the acceptability of peer-based approaches to mental health promotion. The findings can also empirically guide future efforts for systematically building men's peer-based suicide prevention programs.

The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for serious mental illness in community mental health part 1: study protocol for a hybrid type 2 effectiveness-implementation cluster-randomized trial.

BACKGROUND: Serious mental illness (SMI) can have devastating consequences. Unfortunately, many patients with SMI do not receive evidence-based psychological treatment (EBPTs) in routine practice settings. One barrier is poor "fit" between EBPTs and contexts in which they are implemented. The present study will evaluate implementation and effectiveness outcomes of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) implemented in community mental health centers (CMHCs). TranS-C was designed to target a range of SMI diagnoses by addressing a probable mechanism and predictor of SMI: sleep and circadian problems. We will investigate whether adapting TranS-C to fit CMHC contexts improves providers' perceptions of fit and patient outcomes. METHODS: TranS-C will be implemented in at least ten counties in California, USA (N = 96 providers; N = 576 clients), via facilitation. CMHC sites are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each county, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will compare TranS-C (combined Adapted and Standard) with UC-DT on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms. Sleep and circadian problems will also be tested as a mediator between treatment condition (combined TranS-C versus UC-DT) and functional impairment/psychiatric symptoms. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to provider perceptions of fit. Aim 3 will evaluate whether the relation between TranS-C treatment condition (Adapted versus Standard) and patient outcomes is mediated by better provider perceptions of fit in the Adapted condition. Exploratory analyses will (1) compare Adapted versus Standard TranS-C on patient perceptions of credibility/improvement and select PhenX Toolkit outcomes and (2) evaluate possible moderators. DISCUSSION: This trial has the potential to (a) expand support for TranS-C, a promising transdiagnostic treatment delivered to patients with SMI in CMHCs; (b) take steps toward addressing challenges faced by providers in delivering EBPTs (i.e., high caseloads, complex patients, poor fit); and (c) advance evidence on causal strategies (i.e., adapting treatments to fit context) in implementation science. TRIAL REGISTRATION: Clinicaltrials.gov NCT04154631. Registered on 6 November 2019. https://clinicaltrials.gov/ct2/show/NCT04154631.

The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for serious mental illness in community mental health part 2: Study protocol for a hybrid type 2 effectiveness-implementation cluster- randomized trial using train-the-trainer.

Background: Train-the-trainer (TTT) is a promising method for implementing evidence-based psychological treatments (EBPTs) in community mental health centers (CMHCs). In TTT, expert trainers train locally embedded individuals (i.e., Generation 1 providers) to deliver an EBPT, who then train others (i.e., Generation 2 providers). The present study will evaluate implementation and effectiveness outcomes of an EBPT for sleep and circadian dysfunction-the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C)-delivered to CMHC patients with serious mental illness by Generation 2 providers (i.e., trained and supervised within CMHCs via TTT). Specifically, we will investigate whether adapting TranS-C to fit CMHC contexts improves Generation 2 (a) patient outcomes (b) providers' perceptions of fit. Methods: TTT will be implemented in nine CMHCs in California, United States (N= 60 providers; N= 130 patients) via facilitation. CMHCs are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each CMHC, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will assess the effectiveness of TranS-C (combined Adapted and Standard), compared to UC-DT, on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms for Generation 2 patients. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to Generation 2 providers' perceptions of fit. Aim 3 will evaluate whether Generation 2 providers' perceived fit mediates the relation between TranS-C treatment condition and patient outcomes. Exploratory analyses will: (1) evaluate whether the effectiveness of TranS-C for patient outcomes is moderated by generation, (2) compare Adapted and Standard TranS-C on patient perceptions of credibility/improvement and PhenX Toolkit outcomes (e.g., substance use, suicidality); and (3) evaluate other possible moderators. Discussion: This trial has potential to inform the process of (a) embedding local trainers and supervisors to expand delivery of a promising transdiagnostic treatment for sleep and circadian dysfunction, (b) adding to the growing body of TTT literature by evaluating TTT outcomes with a novel treatment and population, and (c) advancing our understanding of providers' perceptions of EBPT 'fit' across TTT generations. Trial registration: Clinicaltrials.gov identifier: NCT05805657. Registered on April 10, 2023. https://clinicaltrials.gov/ct2/show/NCT05805657.

The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for serious mental illness in community mental health part 2: study protocol for a hybrid type 2 effectiveness-implementation cluster-randomized trial using train-the-trainer.

BACKGROUND: Train-the-trainer (TTT) is a promising method for implementing evidence-based psychological treatments (EBPTs) in community mental health centers (CMHCs). In TTT, expert trainers train locally embedded individuals (i.e., Generation 1 providers) to deliver an EBPT, who then train others (i.e., Generation 2 providers). The present study will evaluate implementation and effectiveness outcomes of an EBPT for sleep and circadian dysfunction-the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C)-delivered to CMHC patients with serious mental illness by Generation 2 providers (i.e., trained and supervised within CMHCs via TTT). Specifically, we will investigate whether adapting TranS-C to fit CMHC contexts improves Generation 2 (a) patient outcomes and (b) providers' perceptions of fit. METHODS: TTT will be implemented in nine CMHCs in California, USA (N = 60 providers; N = 130 patients) via facilitation. CMHCs are cluster-randomized by county to Adapted TranS-C or Standard TranS-C. Within each CMHC, patients are randomized to immediate TranS-C or usual care followed by delayed treatment with TranS-C (UC-DT). Aim 1 will assess the effectiveness of TranS-C (combined Adapted and Standard), compared to UC-DT, on improvements in sleep and circadian problems, functional impairment, and psychiatric symptoms for Generation 2 patients. Aim 2 will evaluate whether Adapted TranS-C is superior to Standard TranS-C with respect to Generation 2 providers' perceptions of fit. Aim 3 will evaluate whether Generation 2 providers' perceived fit mediates the relation between TranS-C treatment condition and patient outcomes. Exploratory analyses will (1) evaluate whether the effectiveness of TranS-C for patient outcomes is moderated by generation, (2) compare Adapted and Standard TranS-C on patient perceptions of credibility/improvement and PhenX Toolkit outcomes (e.g., substance use, suicidality), and (3) evaluate other possible moderators. DISCUSSION: This trial has potential to (a) inform the process of embedding local trainers and supervisors to expand delivery of a promising transdiagnostic treatment for sleep and circadian dysfunction, (b) add to the growing body of TTT literature by evaluating TTT outcomes with a novel treatment and population, and (c) advance our understanding of providers' perceptions of EBPT "fit" across TTT generations. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05805657 . Registered on April 10, 2023.

Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers where a primary tissue of origin (TOO) is uncertain. Most patients with CUP have limited treatment options and poor survival outcomes. Immune checkpoint inhibitors (ICIs) can be efficacious in some patients with CUP, but the optimal predictive biomarkers are unknown. We therefore assessed immune and genomic biomarkers as well as predicted TOO in patients with CUP, including a subset treated with ICIs. METHODS: Patients with CUP were subject to gene-expression profiling (GEP) and DNA panel sequencing. Immune and stromal-related gene expression was explored by NanoString, including genes associated with immunotherapy response (IR) in other solid malignancies. ICI responsive cancer types were assigned based on Food and Drug Administration-approved indications, and either detection of a latent primary tumor or the TOO was suspected based on genomics informed pathology review. Tumor mutation burden (TMB) and gene mutations were also assessed. RESULTS: A total of 219 patients with CUP were included, 215 assessed for TOO in a previous study, with the majority (163) receiving both RNA and DNA tests. Of GEP profiled cases, 33% (59/175) had a high IR gene-expression score. Of the DNA sequenced cases, 16% (32/203) had high TMB (>10 mutations/Mb), including two with mismatch repair deficiency. Low correlation was observed between TMB and an IR score (R=0.26, p<0.001). Among 110 CUPs with a latent primary or suspected TOO, 47% (52/110) belonged to ICI-responsive cancer types. More than half of the CUPs had at least one feature that may predict ICI response (high IR score, high TMB, ICI-responsive cancer type). Among patients with CUP treated with ICIs, 8/28 (29%) responded (2 complete responses and 6 partial responses). Among non-responders, 9 had stable and 11 had progressive disease. All responders had a high IR score (7/8) and/or high TMB (3/8), while most (5/8) belonged to ICI-responsive cancer types. These features were detected at a lower frequency in non-responders and mostly in patients with stable disease. CONCLUSIONS: A significant fraction of CUP tumors had genomic features previously associated with ICI response. High IR score was the most sensitive predictive feature of ICI response, warranting evaluation in a larger patient series.

Male-Type Depression Mediates the Relationship between Avoidant Coping and Suicidal Ideation in Men.

Despite known links between men's avoidant coping behaviours (e.g., distraction, denial, substance use) and suicide risk, little research has explored the mechanisms underpinning this relationship. This study sought to examine whether male-type depression symptoms (e.g., anger, aggression, emotion suppression), assessed by the Male Depression Risk Scale, mediate the association between avoidant coping and suicide/self-harm ideation in men. Data were drawn from an online survey of a community sample of 606 Australian men (M age = 50.11 years; SD = 15.00), conducted during the COVID-19 pandemic. Mediation analyses were applied to examine the effect of male-type depression on the association between avoidant coping and suicidal/self-harm ideation, controlling for age, resilience and the experience of two psychosocial stressors during the COVID-19 pandemic (financial stress and government restrictions). Avoidant coping was associated with suicidal/self-harm ideation, r = 0.45, p < 0.001. Results supported a mediating role of male-type depression symptoms in this relationship, R2= 0.29, PM = 0.36, p < 0.001, underscoring the importance of screening for male-type depression symptoms to better identify men at risk of suicidal/self-harm ideation. Results also suggest a need to support men to develop effective coping strategies, particularly in the context of common psychosocial stressors experienced during the COVID-19 pandemic and beyond.

Can integrating the Memory Support Intervention into cognitive therapy improve depression outcome? A randomized controlled trial.

We investigated if improving a patient's memory for the content of their treatment, via the Memory Support Intervention, improves illness course and functional outcomes. The platform for investigating this question was major depressive disorder (MDD) and cognitive therapy (CT). Adults diagnosed with MDD (N = 178) were randomly allocated to CT + Memory Support (n = 91) or CT-as-usual (n = 87). Both treatments were comprised of 20-26, 50-min sessions over 16 weeks. Blind assessments were conducted before and immediately following treatment (post-treatment) and 6 months later (6FU). Patient memory for treatment, assessed with a free recall task, was higher in CT + Memory Support for past session recall at post-treatment. Both treatment arms were associated with reductions in depressive symptoms and functional impairment except: CT + Memory Support exhibited lower depression severity at 6FU (b = -3.09, p = 0.050, d = -0.27), and greater reduction in unhealthy days from baseline to 6FU (b = -4.21, p = 0.010, d = -1.07), compared to CT-as-usual. While differences in illness course and functional outcomes between the two treatment arms were limited, it is possible that future analyses of the type of memory supports and longer follow-up may yield more encouraging outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01790919. Registered October 6, 2016.

Men's anxiety: A systematic review.

AIM: Anxiety disorders are amongst the most commonly diagnosed mental illnesses amongst men; however male-specific anxiety research is lacking. This review explores men's anxiety symptoms and disorders including help-seeking, coping and the role of masculinity. METHOD: Four electronic database searches identified 8,333 citations, with 25 studies meeting inclusion criteria. Nineteen studies employed quantitative methods, five studies reported qualitative research, and one utilised mixed methods. RESULTS: Unique profiles of anxiety, including psychosomatic symptoms, were identified and persisted over extended periods of time. Men commonly reported self-reliance over formal help-seeking, and typically managed anxiety symptoms through problem-based coping. Masculinity was related to anxiety in complex ways; adherence to norms of toughness could be protective against anxiety onset, while adherence to emotional restrictiveness and heterosexual presentation norms were positively associated with anxiety. The experience of, and help-seeking for anxiety transgressed many men's adherence to masculinity norms resulting in significant social and self-stigmas. LIMITATIONS: The anxiety measurement scales utilised were inconsistent across included studies and there was limited scope of research into panic disorders, phobias and agoraphobia. CONCLUSION: Findings demonstrate the enduring nature of anxiety for men and a potential under-reporting of symptoms, especially amongst younger men. To better tailor clinical care and public health resources to the needs of men with anxiety disorders, targeted research examining men's lived experiences of (and coping strategies for) anxiety is essential.

Defining the Supportive Care Needs and Psychological Morbidity of Patients With Functioning Versus Nonfunctioning Neuroendocrine Tumors: Protocol for a Phase 1 Trial of a Nurse-Led Online and Phone-Based Intervention.

BACKGROUND: Online information resources and support have been demonstrated to positively influence the well-being of people diagnosed with cancer. This has been explored in past literature for more common cancers; however, for rare cancers, such as neuroendocrine tumors (NETs), there are little to no support or resources available. Despite relatively good prognoses, the quality of life (QoL) of patients with NETs is significantly lower compared with samples of mixed cancer patients and the general population. Patients with NETs also typically report unclear and difficult pathways of disease management and treatment, given the heterogeneity of the diagnosis. There is a vital need to improve the availability of disease-specific information for this patient group and provide supportive care that is tailored to the unique needs of the NET patient population. OBJECTIVE: This study described the protocol of a study aimed to better understand the outcomes and experiences of patients diagnosed with NETs and to develop and pilot test a nurse-led online and phone-based intervention that will provide tailored supportive care targeted to NET subgroups (functioning vs nonfunctioning). METHODS: This is a multisite cohort with 3 phases, incorporating both quantitative and qualitative data collection. Phase 1 is a mixed methods prospective cohort study of NET patients identifying differences in patient experiences and priority of needs between NET subgroups. Phase 2 utilizes results from phase 1 to develop an online and nurse-led phone-based intervention. Phase 3 is to pilot test and evaluate the intervention's acceptability, appropriateness, and feasibility. RESULTS: Currently, the project is progressing through phase 1 and has completed recruitment. A total of 138 participants have been recruited to the study. To date, patient-reported outcome data from 123 participants at baseline and 87 participants at 6-month follow-up have been collected. Of these, qualitative data from semistructured interviews from 35 participants have also been obtained. Phase 2 and phase 3 of the project are yet to be completed. CONCLUSIONS: Limited research for patients with NETs suggests that QoL and patient experiences are significantly impaired compared with the general population. Furthermore, past research has failed to delineate how the clinical variability between those with functioning and nonfunctioning NETs impacts patient supportive care needs. This study will improve on the availability of disease-specific information as well as informing the design of a nurse-led online and phone-based supportive care intervention tailored for the unique needs of the NET patient population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14361.

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.