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Objectives: Farmers are faced with many stressors, along with numerous barriers to accessing traditional forms of mental health support. The ifarmwell online intervention was co-designed with farmers and is informed by Acceptance and Commitment Therapy to equip farmers with transferable coping strategies, particularly to help them cope with circumstances beyond their control. We aimed to evaluate the effect of ifarmwell on farmers’ short- and long-term distress and mental wellbeing. Methods: Australian farmers (21–73 years) who registered on www.ifarmwell.com.au completed measures at the commencement of module 1 (N = 228), the end of the intervention (N = 77) and 6-months post-intervention (N = 61). Primary outcomes included distress (Kessler Psychological Distress Scale) and mental wellbeing (Mental Health Continuum – Short Form). We also examined the relationship between distress, mental wellbeing, neuroticism (Quickscales-R) and ACT-based psychological mechanisms; psychological inflexibility (Acceptance and Action Questionnaire-II), cog-nitive fusion (Cognitive Fusion Questionnaire), believability of automatic thoughts (Automatic Thoughts Questionnaire-B), coping via acceptance (4 items from the situational COPE) and mind-fulness (Five Facet Mindfulness Questionnaire-Short Form). Secondary outcomes of acceptability (Client Satisfaction Questionnaire-8) and usability (System Usability Scale) were also explored. Results: Pre- to post-intervention, farmers’ distress decreased and mental wellbeing increased. These effects were maintained at 6-month follow-up. Changes in these outcomes were greatest for participants who entered the intervention with high baseline distress (^β= −0.59, 95%CI =[−0.70, −0.47]) and low mental wellbeing (^β= −0.33, 95%CI = [−0.47, −0.19]). Decreases in distress and increases in mental wellbeing were associated with decreases in psychological inflexibility, cognitive fusion, and believability of thoughts, and increases in coping via acceptance and mindfulness. Levels of satisfaction (M = 26.92/32) and usability (M = 84.70/100) were high, and 94.6% of participants said they would recommend ifarmwell to a friend in need of similar advice and tools. Conclusions: ifarmwell is an effective and usable intervention that is likely to help farmers reduce their levels of distress and improve their mental wellbeing, by improving their psychological flexibility, ability to focus on the present and accept things beyond their control, as well as by reducing the extent to which they believe unhelpful thoughts. Refereed/Peer-reviewed

Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 ( ω-3) PUFAs and astaxanthin, may be a safe and effective alternative treatment.This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers.Healthy adults (n = 235, 40-65 y old, BMI18.5 to35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0-100). Outcomes were assessed at baseline, 3 mo, and 6 mo.Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: -5.18; 95% CI: -10.0, -0.32; P = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: -6.45; 95% CI: -12.1, -0.9 and -4.67; 95% CI: -9.26, -0.05, respectively; P 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups.Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA.This trial was registered at clinicaltrials.gov as NCT03483090.

Results of lipid association analyses

Supplementary Figures S1-S6

Patient and sample clinical characteristics

Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting.Significance:This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.

Objective To determine the association of combined parental preconception overweight and obesity on infant birthweight. Design Retrospective study of fresh in vitro fertilization or intracytoplasmic sperm injection cycles (2009–2017). Setting Repromed, South Australia, assisted reproductive technology clinic. Patients Couples undergoing in vitro fertilization/intracytoplasmic sperm injection insemination with their own gametes and transfer of a fresh single blastocyst (N = 1,778). Intervention(s) None. Main Outcome Measures Parental body mass index (BMI) was recorded prior to cycle initiation. Infant birthweight was recorded at delivery. The impact of parental obesity and their interaction on first singleton term (≥37 weeks’ gestation) birthweight was assessed using linear regressions assessing nonlinearity and a pairwise linear interactions. Results In the base model where parental BMI is assumed linear, there was strong evidence for higher birthweight with increasing maternal BMI (11.2 g per maternal kg/m2; 95% confidence interval, 7.2, 15.1) but not paternal BMI. The inclusion of a pairwise linear interaction indicated that paternal BMI attenuates the positive association between maternal BMI and infant birthweight (interaction −0.88; 95% confidence interval, −1.49, −0.27). The inclusion of nonlinear maternal BMI terms did not change the conclusions. Conclusions Increases in the mean infant birthweight associated with maternal obesity are attenuated when the father is obese. While maternal BMI contributed more to the mean infant birthweight than paternal BMI, a couple-centered approach to preconception health advice is recommended, given the documented relationships between parental obesity and childhood weight beyond infancy. Further studies in both assisted reproductive technology and general population cohorts assessing the parental BMI interaction on infant birthweight are warranted.

BACKGROUND Background: Only a minority of adult males who experience depression or anxiety receive any formal help from a healthcare professional for these issues. While psychotherapeutic e-mental health interventions may circumvent or reduce many of the barriers males experience when accessing mental health care, the effects of these interventions in male populations have not been evaluated. OBJECTIVE Objectives: (1) Synthesise the characteristics of psychotherapeutic e-mental health interventions for depression or anxiety that have been trialled and evaluated in male populations; (2) synthesise and meta-analyse the effects of these interventions on depression and anxiety outcomes in males, including examining the influence of participant, intervention, and study characteristics. METHODS Methods: Systematic searches (January 2000-October 2020) of six online research databases, manual reference list searching, and citation searches of included articles. Study quality was assessed using the Qualsyst tool, with a minimum total score of 0.55 prespecified for inclusion. Data were narratively synthesised and, where possible, meta-analysed. RESULTS Results: Seven papers comprising 552 male participants were included. A total of 177 studies were excluded because although they met all other inclusion criteria, they did not present analysable data on male participants. With a lowest total score of 0.85, study quality was high and no exclusions were made due to poor quality. Four studies used a single-arm pre-post design and three were randomised controlled trials (all with inactive/care as usual control conditions); five studies were focused on treating existing symptoms, while two focused on prevention. The seven studied interventions varied in content, length, and format. Only one intervention was classified as gender sensitive, having been designed specifically for male needs. All of the studies used non-gendered, self-report symptom measures to measure the effects of their intervention. All three randomised controlled trials detected no post-trial difference in depression symptoms between male intervention and male control participants. All four treatment studies presenting pre-post data reported post-intervention improvements in depression or social anxiety symptoms; this was supported by our meta-analysis of the two pre-post design depression treatment studies, which found a medium-sized, positive effect of treatment interventions on depression symptoms in pre-post data (g=0.64, p CONCLUSIONS Conclusions: Limited data indicate that psychotherapeutic e-mental health treatment interventions resulted in pre- to post-intervention improvements in male depression symptoms; superior outcomes were not seen when compared to inactive/care as usual control conditions. There is urgent need for consideration of gender and sex throughout the development, evaluation, and dissemination of these interventions for males, and for additional information on their effects. CLINICALTRIAL

Time-restricted feeding (TRF) initiated early during the dark phase prevents the metabolic consequences of a high-fat diet in rodent models. However, the metabolic consequences of delaying the initiation of TRF, akin to breakfast skipping in humans, is unclear. We assigned 8-week-old male C57BL/6J mice (n = 192) to chow or high-fat diet ad libitum (AL) for 4 weeks, before randomization to continue AL or 10 h of TRF, initiated at lights off (TRFe) or 4-h after lights off (TRFd) for a further 8 weeks. Oral glucose tolerance tests (1 g/kg), metabolic monitoring and body composition by echoMRI were performed, and tissues were collected at six time points. TRF reduced weight and fat mass vs AL, with a greater reduction in TRFe vs TRFd. TRF improved glucose tolerance and protected mice from high-fat diet-induced hepatosteatosis vs AL, with no difference between TRFe and TRFd. TRF increased the amplitude of Bmal1, Cry1, Per2, Nampt, and Nocturnin mRNA levels in liver. A phase delay in Bmal1, Cry1, Per2, Reverbα, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight benefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the translational potential of this dietary approach in humans.

Background: Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case-control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-minute questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded within the different incentive groups. Methods: We conducted this randomised study within a case-control cross-sectional study aiming to identify the social-ecological factors influcing treatment discontinuation in prostate cancer patients. A total of 238 participants from the cross-sectional study were randomised to receive one of two unconditional incentives (n=121 received AUD$10, n=117 received AUD$20) with the study materials (consent form and survey). Results: Overall, 113 (47%) responded; n=61/121 (50.4%) in the AUD$10 group, and n=52/117 (44.4%) in the AUD$20 group. No difference was found in response rates by incentive group (odds ratio 1.27, 95% CI=0.76-2.12, p=0.36). Additionally, there were no differences in the demographics of the responders vs. non-responders within each incentive group (all p>0.05). Conclusions: Unlike previous research, we were unable to show that higher monetary incentives were more effective for increasing response rates. An AUD$20 unconditional incentive may be no more effective than a lesser amount for encouraging prostate cancer survivors to participate in research involving long questionnaires. Future research should consider the cost-benefits of providing large unconditional incentives, as non-responses will result in lost resources perhaps better utilised in other engagement strategies.

Purpose Reduced hand grip strength (HGS) is associated with poorer health in chronic conditions, yet there has been little research examining the association with hand grip strength and obstructive sleep apnea (OSA). Further, these studies have not examined, nor adjusted, for muscle mass. The aim of this study was to determine associations between OSA indices, HGS, muscle mass, and fat mass. Participants and methods A total of 613 participants (age range 41-88, BMI 28.6 ± 4.3) from the population-based Men Androgen Inflammation Lifestyle Environment and Stress Study underwent in-home overnight polysomnography, assessment of dominant and non-dominant HGS, and dual x-ray absorptiometry to determine whole body muscle mass and fat mass. Linear models determined cross-sectional associations of polysomnographic-derived OSA indices with hand grip strength, muscle mass, and fat mass, whilst adjusting for lifestyle information (income, smoking status, diet, self-reported physical activity), blood sample derived testosterone and systemic inflammation (C-reactive protein), cardiometabolic health (cardiovascular disease, hypertension, type 2 diabetes), and depression. Results In adjusted models, reduced dominant HGS was associated with lower oxygen nadir (unstandardised β [B] = 0.19, 95% confidence interval [CI] 0.08 to 0.29), greater time spent below 90% oxygen saturation (B = -0.08, 95% CI -0.14 to -0.02), and increased apnea duration (B = -0.3, 95% CI -0.23 to -0.02). By contrast, there were no associations between HGS and both AHI and REM AHI. Fat mass was consistently associated with worsening OSA indices, whereas muscle mass demonstrated no associations with any OSA index. Conclusion Our findings suggest impairments in HGS may be related to fat infiltration of muscle, hypoxemia-induced reductions in peripheral neural innervation, or even endothelial dysfunction, which is a common outcome of hypoxemia. Longitudinal data are needed to further examine these hypotheses and establish if reduced grip strength in patients with OSA is associated with long-term adverse health outcomes.

Objective To examine prostate cancer (PCa) survivors’ sexual help-seeking intentions, behaviours, and unmet needs. Methods In this prospective cohort study, men who underwent active, non-hormonal treatment completed baseline (N = 558) and 6-month follow-up (N = 387) questionnaires. Theory of planned behaviour (TPB) constructs (sexual help-seeking intention, perceived behavioural control (PBC), subjective norm, attitude), masculine values (e.g., sexual importance/priority, emotional self-reliance), sex life and functioning, sexual supportive care needs, distress (anxiety, depression), and sexual help-seeking behaviour were assessed. Results Most men (M age = 64.6 years; M years post-diagnosis = 4.0) received prostatectomy (93%), reported severe erectile dysfunction (52%), ≥ 1 unmet sexual care need (66%), and sought help from a doctor (baseline 52%, follow-up 42%). Sexual care needs were significantly associated with poorer erectile function, reduced satisfaction with sex-life, valuing sex as important/integral to identity (masculine values), and increased depression (p ≤ 0.001). Sexual help-seeking intentions were significantly associated with valuing sex as important/integral to identity, recent help-seeking, greater confidence/control, perceiving support from important others, and positive attitudes, for sexual help-seeking (p < 0.001). Significant predictors of sexual help-seeking (follow-up) were baseline intentions, recent help-seeking (p < 0.001), and increased anxiety (p < 0.05). Conclusions Men’s unmet sexual care needs, sexual help-seeking intentions, and behaviour appear driven by the importance/value attributed to sex, distress, positive feelings, support from others, and confidence for help-seeking. Psychosocial providers are well-placed to address men’s concerns, yet few sought their assistance. Interventions to improve men’s access to effective sexual care are needed, particularly focused on reframing masculine values about the importance of sex and leveraging TPB-based predictors of help-seeking.

Objectives:We aimed to assess the incidence of obstructive sleep apnoea (OSA) in people with schizophrenia, to explore clinical associates with OSA and how well OSA screening tools perform in this population.Methods:All patients registered in a community outpatient Clozapine clinic, between January 2014 and March 2016, were consecutively approached to participate. Participants were screened for OSA using at home multichannel polysomnography (PSG) and were diagnosed with OSA if the apnoea-hypopnoea index (AHI) was >10 events/hr. Univariate comparison of participants to determine whether AHI > 10 events/hr was associated with demographic factors, anthropometric measures and psychiatric symptoms and cognition was performed. The sensitivity, specificity, positive predictive value and negative predictive value of the commonly used sleep symptoms scales and OSA screening tools were also determined.Results:Thirty participants were recruited, 24 men and 6 women. Mean age was 38.8 (range: 25–60), and mean body mass index (BMI) was 35.7 (range 19.9–62.1). The proportion of participants with OSA (AHI > 10 events/hr) was 40%, 18 (60%) had no OSA, 4 (13%) had mild OSA (AHI 10.1–20), zero participants had moderate OSA (AHI 20.1–30) and 8 (27%) had severe OSA (AHI > 30). Diagnosis of OSA was significantly associated with increased weight, BMI, neck circumference and systolic blood pressure. Diagnosis of OSA was not significantly associated with Positive and Negative Symptoms Scale, Montgomery Asperger’s Depression Rating Scale, Personal and Social Performance scale or Brief Assessment of Cognition for Schizophrenia scores. All OSA screening tools demonstrated poor sensitivity and specificity for a diagnosis of OSA.Conclusion:OSA was highly prevalent in this cohort of people with schizophrenia and was associated with traditional anthropometric OSA risk factors.

Background Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study ( D aily versus I ntermittent R estriction of E nergy: C ontrolled T rial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. Methods Anticipated 260 non-diabetic men and women aged 35–75 years, BMI 25−50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. Discussion This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes.

Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.

Background Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of small monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case–control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-min questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded within the different incentive groups. Methods We conducted this randomised study within a case–control cross-sectional study aiming to identify the social-ecological factors influencing treatment discontinuation in prostate cancer patients. A total of 238 participants from the cross-sectional study were randomised to receive one of two unconditional incentives (n = 121 received AUD$10, n = 117 received AUD$20) with the study materials (consent form and survey). Results Overall, 113 (47%) responded; n = 61/121 (50.4%) in the AUD$10 group, and n = 52/117 (44.4%) in the AUD$20 group. No evidence of a difference was found in response rates by incentive group (odds ratio 1.27, 95% CI = 0.76–2.12, p = 0.36). Additionally, there were no evident differences in the demographics of the responders vs. non-responders within each incentive group (all p > 0.05). Conclusions Unlike previous research, we were unable to show that higher monetary incentives were more effective for increasing response rates. An AUD$20 unconditional incentive may be no more effective than a lesser amount for encouraging prostate cancer survivors to participate in research involving long questionnaires. Future research should consider the cost-benefits of providing large unconditional incentives, as non-responses will result in lost resources perhaps better utilised in other engagement strategies.

Objectives: To explore the personal and/or medical reasons patients on active surveillance (AS) have, or consider having, further definitive treatment for their prostate cancer. Research suggests up to 50% of patients on AS will discontinue within 5 years, though reasons for discontinuation from the patient's perspective is under-explored. Methods: Prostate cancer patients who were or had been on AS for at least 6 months were recruited. A questionnaire assessed reasons for receiving/considering definitive treatment and the extent to which reasons were personal or medical. Clinical information was extracted from a state-level population registry. A subset of participants were interviewed to further explore questionnaire responses. Results: One-hundred and-three individuals completed the survey; 33 were also interviewed. Fifty-four survey participants (52%) had discontinued AS for definitive treatment. Common reasons for discontinuation were evidence of disease progression, doctor recommendation, desire to act, and fear of progression. Many participants who considered or had treatment reported weighing medical and personal factors equally in their decision. Interview participants described strongly considering any amount of disease progression and personal factors such as fear of progression, family concerns, and adverse vicarious experiences when deciding whether to pursue treatment. Conclusion: Both medical and personal factors are considered when deciding whether to discontinue AS. Identifying predictors of discontinuation is essential for informing supportive care services to improve AS management. Refereed/Peer-reviewed

Purpose: While prostate cancer survivors experience unmet supportive care needs (USCNs) after definitive treatments, no study has measured USCNs during active surveillance (AS). This mixed-methods study aimed to identify and explore the USCNs and psychological wellbeing of AS patients.Methods: Patients 18+ years diagnosed with prostate cancer, who had been on AS for ≥6 months, were invited to complete a survey measuring USCNs, general and prostate cancer specific anxiety, and depression. A purposefully selected subset was also interviewed to explore USCNs and how needs during AS were addressed. Semi-structured interviews were transcribed verbatim and thematically analysed. Results: One hundred and three participants (n=47 currently on AS, n=54 on/had subsequent treatment, n=2 ceased all care) completed the survey, and 33 were also interviewed. Although most USCNs were considered low/moderate, 20% of participants reported high unmet informational needs around receiving information about monitoring and their test results. USCNs related to patient care (e.g., access to services in rural areas or after hours) and sexuality were also discussed in interviews. Anxiety, depression, and prostate cancer specific anxiety were generally very low. Fear of cancer progression/recurrence was the highest scoring prostate cancer specific worry and was frequently mentioned by interview participants.Conclusions: While unmet needs, anxiety and depression were generally low, one in five patients during AS experience unmet needs in psychological, physical, patient care, information, and sexual domains. Health professionals should be aware of common USCNs and offer appropriate support to address potential needs.

Recommendations for staging newly diagnosed prostate cancer patients vary between guidelines and literature.Our objective was to validate and compare prediction models selecting newly diagnosed prostate cancer patients for bone scan staging. To achieve this, we validated eleven models in a population-based cohort of 10,721 patients diagnosed with prostate cancer between 2005 and 2019. The primary outcome was net-benefit. This was assessed at different balances of conservatism and tolerance, represented by preference ratio and number-willing-to-test (NWT). Secondary outcomes included calibration slope, calibration-in-the-large (intercept), and discrimination measured by Area-under-the-receiver-operator-characteristics curve (AUC).For preference ratios less than 1:39 (NWT greater than 40), scanning everyone provided greater net-benefit than selective staging. For preference ratios 1:39 to 3:97 (NWT 33-40), the European Association of Urology (EAU) 2020 guideline recommendation was the best approach. For preference ratios 3:97-7:93 (NWT 14-33), scanning EAU high-risk patients only was preferable. For preference ratios 7:93-1:9 (NWT 10-13), scanning only Gnanapragasam Group 5 patients was best. All models had similar fair discrimination (AUCs 0.68-0.80), but most had poor calibration.We identified three selective staging strategies that outperformed all other approaches but did so over different ranges of conservatism and tolerance. Scanning only EAU high-risk patients provided the greatest net-benefit over the greatest range of preference ratios and scenarios, but other options may be preferable depending upon the local healthcare system's degree of conservatism and tolerance.

Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting. Significance: This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.

BACKGROUND Digital health interventions such as tailored websites are emerging as valuable tools to provide individualized exercise and behavioral change information for individuals diagnosed with cancer. OBJECTIVE The aim of this study is to investigate and iteratively refine the acceptability and usability of a web-based exercise intervention (ExerciseGuide) for men with metastatic prostate cancer and determine how well individuals can replicate the video-based exercise prescription. METHODS A laboratory-based multi-methods design was used, incorporating questionnaires, think-aloud tests, interviews, and movement screening among 11 men aged 63 to 82 years with metastatic prostate cancer. Overall, 9 participants were undergoing androgen deprivation therapy, and 2 were completing chemotherapy. Data were collected in two waves, with changes made for quality improvement after participant 5. RESULTS The intervention’s usability score was deemed moderate overall but improved after modifications (from 60, SD 2.9 to 69.6, SD 2.2 out of 100). Overall, the participants found the intervention acceptable, with scores improving from wave 1 (24.2, SD 1.1 out of 30) to wave 2 (26.3, SD 2.1 out of 30). The personalized multimodal exercise prescription and computer-tailored education were seen as valuable. After wave 1, website navigation videos were added, medical terminology was simplified, and a telehealth component was included after expert real-time telehealth support was requested. Wave 2 changes included the added variety for aerobic exercise modes, reduced computer-tailoring question loads, and improved consistency of style and grammar. Finally, the participants could replicate the resistance exercise videos to a satisfactory level as judged by the movement screen; however, additional technique cueing within the videos is recommended to address safety concerns. CONCLUSIONS The acceptability and usability of ExerciseGuide were deemed satisfactory. Various problems were identified and resolved. Notably, the participants requested the inclusion of personalized expert support through telehealth. The resistance training algorithms were shown to provide appropriate content safely, and the users could replicate the exercise technique unaided to a satisfactory level. This study has optimized the ExerciseGuide intervention for further investigation in this population. CLINICALTRIAL Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001978257; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001978257

ObjectivesTo examine the relationship between depression burden, health service utilisation and depression diagnosis in community-based men.DesignProspective cohort study.SettingCommunity-based.ParticipantsMen aged 35–80 years at recruitment (2002–2005), randomly selected from the northern and western suburbs of Adelaide, Australia, without depression at baseline, who attended follow-up visits (2007–2010) (n=1464).Primary and secondary outcome measuresDepression symptoms were categorised into high burden (total score of ≥13 for the Beck Depression Inventory (BDI) or ≥10 for the Centre for Epidemiologic Studies Depression Scale (CES-D) or low burden (ResultsFrequent attendance and depression diagnosis was more common in men with a high than low burden of depression symptoms (45.9% vs 29.3%–18.7% vs 1.9%, pConclusionsMen with a high burden of depression symptoms have commensurate use of health services when compared with those with a low burden, but only half report a physician diagnosis of depression. Undiagnosed depression led to a higher usage of medical and prescription services.

PURPOSE: To determine if the use of ICSI in women of advanced maternal age with non-male factor infertility increases chances of live birth. METHODS: Retrospective data analysis of 10 years of cycle data from a single Australian IVF clinic (Repromed). First cycle patients only of an advanced maternal age (≥ 35 years) with non-male factor infertility utilising standard IVF or ICSI insemination and having at least three oocytes collected at egg pick up were assessed for live birth following transfer of single genetically unscreened blastocyst (N = 577). Subanalysis of clinical pregnancy, miscarriage, fertilisation, embryo utilisation rate and having a blastocyst for transfer were considered. Unadjusted, covariate adjusted and propensity score weighted analysis were performed. RESULTS: The use of standard IVF insemination in women ≥ 35 years with non-male factor infertility increased the chance of a live birth compared with ICSI insemination (unadjusted OR = 2.72, 95% CI [1.78, 4.17]; adjusted OR = 2.64, 95% CI [1.64, 4.27] and weighted OR = 2.26, 95% CI [1.72, 2.98] 31% vs 14%). All other outcomes (fertilisation rate, embryo utilisation, blastocyst for embryo transfer and miscarriage rate) were unaffected. CONCLUSION: In couples with advanced maternal age and non-male factor infertility, standard IVF insemination appears to increase the chance of a live birth compared with ICSI. As such, the results of this study support the use of routine IVF as the preferred insemination technique for older women in non-male factor infertility. However, future randomised controlled trials are still required to assess this policy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02026-8.

Introduction Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. Despite this, many individuals do not engage in sufficient exercise to gain the benefits. There are many barriers, which limit the uptake of face-to-face exercise in this population including lack of suitable facilities, remoteness, and access to experts, significant fatigue, urinary incontinence and motivation. Technology-enabled interventions offer a distance-based alternative. This protocol describes a pilot two-armed randomised controlled study that will investigate the feasibility and preliminary efficacy of an online exercise and behavioural change tool (ExerciseGuide) amongst individuals with metastatic prostate cancer. Methods Sixty-six participants with histologically diagnosed metastatic prostate cancer will be randomised into either the 8-week intervention or a wait-list control. The intervention arm will have access to a tailored website, remote supervision, and tele-coaching sessions to enhance support and adherence. Algorithms will individually prescribe resistance and aerobic exercise based upon factors such as metastasis location, pain, fatigue, confidence and current exercise levels. Behavioural change strategies and education on exercise benefits, safety and lifestyle are also tailored through the website. The primary outcome will be intervention feasibility (safety, usability, acceptability, and adherence). Secondary exploratory outcomes include changes in physical activity, quality of life, sleep, and physical function. Outcomes will be measured at baseline and week 9. Discussion The study aims to determine the potential feasibility of an online remotely monitored exercise intervention developed for individuals with metastatic prostate cancer. If feasible, this pilot intervention will inform the design and implementation of further distance-based interventions. Trial registration ANZCTR, ACTRN12614001268639. Registered 10 December 2018, https://anzctr.org.au/ACTRN12618001979246.aspx

Background Digital health interventions such as tailored websites are emerging as valuable tools to provide individualized exercise and behavioral change information for individuals diagnosed with cancer. Objective The aim of this study is to investigate and iteratively refine the acceptability and usability of a web-based exercise intervention (ExerciseGuide) for men with metastatic prostate cancer and determine how well individuals can replicate the video-based exercise prescription. Methods A laboratory-based multi-methods design was used, incorporating questionnaires, think-aloud tests, interviews, and movement screening among 11 men aged 63 to 82 years with metastatic prostate cancer. Overall, 9 participants were undergoing androgen deprivation therapy, and 2 were completing chemotherapy. Data were collected in two waves, with changes made for quality improvement after participant 5. Results The intervention’s usability score was deemed moderate overall but improved after modifications (from 60, SD 2.9 to 69.6, SD 2.2 out of 100). Overall, the participants found the intervention acceptable, with scores improving from wave 1 (24.2, SD 1.1 out of 30) to wave 2 (26.3, SD 2.1 out of 30). The personalized multimodal exercise prescription and computer-tailored education were seen as valuable. After wave 1, website navigation videos were added, medical terminology was simplified, and a telehealth component was included after expert real-time telehealth support was requested. Wave 2 changes included the added variety for aerobic exercise modes, reduced computer-tailoring question loads, and improved consistency of style and grammar. Finally, the participants could replicate the resistance exercise videos to a satisfactory level as judged by the movement screen; however, additional technique cueing within the videos is recommended to address safety concerns. Conclusions The acceptability and usability of ExerciseGuide were deemed satisfactory. Various problems were identified and resolved. Notably, the participants requested the inclusion of personalized expert support through telehealth. The resistance training algorithms were shown to provide appropriate content safely, and the users could replicate the exercise technique unaided to a satisfactory level. This study has optimized the ExerciseGuide intervention for further investigation in this population. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001978257; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001978257

Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Herein, we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n=21), independent tissues (n=47), and primary prostate explants cultured with a clinical AR antagonist, enzalutamide (n=43). Significant differences in lipid composition were detected and spatially visualized in tumors compared to matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and PL composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting of altered tumor-related lipid features, via inhibition of acetyl CoA carboxylase 1, significantly reduced cellular proliferation in tissue explants (n=13). This first characterization of the prostate cancer lipidome in clinical tissues revealed enhanced fatty acid synthesis, elongation and desaturation as tumor-defining features, with potential for therapeutic targeting.

Background: Web-based computer-tailored interventions can assist prostate cancer survivors to become more physically active by providing personally relevant behaviour change support. This study aimed to explore how changing the website architecture (free choice vs. tunnelled) impacted engagement within a physical activity computer-tailored intervention targeting prostate cancer survivors. Methods: On a 2:2:1 ratio, 71 Australian prostate cancer survivors with local or locally advanced disease (mean age: 66.6 years &plusmn, 9.66) were randomised into either a free-choice (N = 27), tunnelled (N = 27) or minimal intervention control arm (N =17). The primary outcome was differences in usage of the physical activity self-monitoring and feedback modules between the two intervention arms. Differences in usage of other website components between the two intervention groups were explored as secondary outcomes. Further, secondary outcomes involving comparisons between all study groups (including the control) included usability, personal relevance, and behaviour change. Results: The average number of physical activity self-monitoring and feedback modules accessed was higher in the tunnelled arm (M 2.6 SD 1.3) compared to the free-choice arm (M 1.5 SD 1.4), p = 0.01. However, free-choice participants were significantly more likely to have engaged with the social support (p = 0.008) and habit formation (p = 0.003) &lsquo, once-off&rsquo, modules compared to the standard tunnelled arm. There were no other between-group differences found for any other study outcomes. Conclusion: This study indicated that website architecture influences behavioural engagement. Further research is needed to examine the impact of differential usage on mechanisms of action and behaviour change.

Objectives: A randomised controlled trial was undertaken to compare the efficacy of topical Calendula officinalis (Calendula) versus standard of care (Sorbolene: 10% glycerine in cetomacragol cream) in reducing the prevalence of radiation-induced dermatitis in women undergoing breast cancer radiotherapy. Methods: A total of 271 women were screened and 82 were randomised. The primary outcome was prevalence of acute radiation-induced dermatitis (RTOG grade 2+) assessed at multiple skin sites. A chi-squared test was conducted for the primary outcome with a worst-case scenario imputation. Results: The recruitment target (n = 178) was not achieved. A total of n = 81 participants were analysed (n = 40 Calendula; n = 41 Sorbolene). There was no detectable difference in prevalence of radiation-induced dermatitis grade 2+ between the Calendula (53%) and Sorbolene (62%) groups (primary analysis OR = 0.87, 95% CI: [0.36, 2.09], P = 0.92; covariate adjusted complete case analysis OR 0.40, 95% CI: [0.13, 1.20], P = 0.10). Conclusion: This randomised controlled trial showed no difference between Calendula and standard of care (Sorbolene) for the prevention of radiation-induced dermatitis. However, the study was underpowered (limited recruitment) for the primary comparison. Refereed/Peer-reviewed

Purpose Reduced hand grip strength (HGS) is associated with poorer health in chronic conditions, yet there has been little research examining the association with hand grip strength and obstructive sleep apnea (OSA). Further, these studies have not examined, nor adjusted, for muscle mass. The aim of this study was to determine associations between OSA indices, HGS, muscle mass, and fat mass. Participants and Methods A total of 613 participants (age range 41–88, BMI 28.6 ± 4.3) from the population-based Men Androgen Inflammation Lifestyle Environment and Stress Study underwent in-home overnight polysomnography, assessment of dominant and non-dominant HGS, and dual x-ray absorptiometry to determine whole body muscle mass and fat mass. Linear models determined cross-sectional associations of polysomnographic-derived OSA indices with hand grip strength, muscle mass, and fat mass, whilst adjusting for lifestyle information (income, smoking status, diet, self-reported physical activity), blood sample derived testosterone and systemic inflammation (C-reactive protein), cardiometabolic health (cardiovascular disease, hypertension, type 2 diabetes), and depression. Results In adjusted models, reduced dominant HGS was associated with lower oxygen nadir (unstandardised β [B] = 0.19, 95% confidence interval [CI] 0.08 to 0.29), greater time spent below 90% oxygen saturation (B = −0.08, 95% CI −0.14 to −0.02), and increased apnea duration (B = −0.3, 95% CI −0.23 to −0.02). By contrast, there were no associations between HGS and both AHI and REM AHI. Fat mass was consistently associated with worsening OSA indices, whereas muscle mass demonstrated no associations with any OSA index. Conclusion Our findings suggest impairments in HGS may be related to fat infiltration of muscle, hypoxemia-induced reductions in peripheral neural innervation, or even endothelial dysfunction, which is a common outcome of hypoxemia. Longitudinal data are needed to further examine these hypotheses and establish if reduced grip strength in patients with OSA is associated with long-term adverse health outcomes.

Refereed/Peer-reviewed Objective: To identify the modifiable psychological and behavioural coping strategies associated with low levels of psychological distress, independent of more stable personality and demographic factors, in a sample of farmers who reported being exposed to a recent stressful event during an extended drought. Results In the final multivariable model, distress was elevated among individuals reporting higher neuroticism and behavioural disengagement, and lower in individuals reporting greater use of acceptance. These 3 variables explained 44% of the variance in distress. Design/setting/participants: Three hundred and nine South Australian, drought-affected grain, sheep and/or cattle farmers completed printed or online questionnaires. Only those who reported experiencing a stressful event in the past month that they rated >= 7 on a scale ranging from 1 (not stressful at all) to 10 (extremely stressful) were included in the analyses (n = 175, 65.06%). Participants ranged in age from 24 to 85 years and 40% were female. Main outcome measures: Psychological distress was measured using the Kessler Psychological Distress Scale, and coping strategies were measured using a situational version of the COPE inventory. Five personality factors (extraversion, neuroticism, openness, conscientiousness and agreeableness) were assessed using the Quickscales-R. Results: In the final multivariable model, distress was elevated among individuals reporting higher neuroticism and behavioural disengagement, and lower in individuals reporting greater use of acceptance. These 3 variables explained 44% of the variance in distress. Conclusion: Farmers recently exposed to a significant stressor, who used acceptance as a coping strategy, did not engage in behavioural disengagement and scored low on neuroticism, were least likely to experience distress. Given the stability of personality factors, interventions that foster farmers' use of acceptance and prevent behavioural disengagement as coping strategies might assist them with the management of future stressors, particularly in times of drought.

Background and objectiveTraditional masculinity is characterised by traits of independence, toughness, assertiveness, competitive-ness and physical competence. Multiple factors modulate the expression of masculinity, including age, social class, ethnicity and occupation. While there is a perception that physiological testosterone concen-tration impacts self-perceived masculinity in men, there are limited supporting data. This study aimed to examine the relationship between testosterone concentration and self-perceived masculinity as measured by the Masculinity in Chronic Disease Inventory (MCD-I), controlling for health-related and biopsycho-social factors in community-dwelling, middle-aged to elderly men.Materials and methodsParticipants were drawn from a longitudinally followed cohort (N=1195) of men participating in the Florey Adelaide Male Aging Study based in Adelaide, Australia. A final sample of 460 (mean age 65.15, stan-dard deviation 9.72) men consisted of those with serum testosterone concentrations measured at wave one (2002–2005) and wave two (2007–2010), and who, in 2017, completed the Masculinity in Chronic Disease Inventory questionnaire and provided information related to demographics, medical conditions, health and lifestyle behaviours.Adjusted multivariable regression analyses were undertaken to determine the relationship between serum testosterone concentration at wave 2 and MCD-1 total masculinity score and sub-scores. Given the temporal difference between the testosterone concentration assessment and MCD-1 completion, a further analysis was performed including participants with a stable serum testosterone concentration over a 5-year period.ResultsThere was no association between serum testosterone concentration and MCD-1 total masculinity score (p = 0.54) or sub-scores (p = 0.12–0.85). There was also no association between testosterone concentration and total masculinity score in men with stable serum testosterone over time (p = 0.35). Testosterone con-centration was associated with serum sex-hormone-binding globulin (SHBG) concentration (p < 0.001), age (p < 0.001), waist circumference (p < 0.001) and a history of diabetes (p = 0.021). Total masculinity score was lower in men without a partner (widowed p < 0.013, separated/divorced p < 0.019), a history of anxiety (p = 0.036) and moderate (p = 0.05) to severe erectile dysfunction (p < 0.001).ConclusionThis study provides evidence against the perception that physiological testosterone concentration impacts self-perceived masculinity. Rather, in middle-aged to older men, self-perceived masculinity is abrogated by psychosocial factors and chronic physical disorders.

Objective: This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition. Methods: Women with overweight (n=88; 50±1 years, BMI 32.3±0.5 kg/m2) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic-euglycemic clamp, weight, body composition, and plasma markers were assessed following a "fed" day (12-hour fast) and a 24-hour fast (IF only). Results: displayed greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P≤0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24-hour fast transiently reduced insulin sensitivity. Conclusions: When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss.

Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (BMI, waist circumference (WC)) and serum hormone (serum testosterone, estradiol (E2)) PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis. Mixed-effects regressions and mediation analyses adjusting for hormonal and volumetric factors explore the potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels were lower in men with greater WC (P = 0.001). In a multivariable model including WC, age, E2/testosterone and PlasV as predictors, no statistically significant associations were observed between with PSA and either WC (P = 0.36) or PlasV (P = 0.49), while strong associations were observed with both E2/testosterone (P P P = 0.31), while when E2/testosterone is a mediator, the ACME explained roughly 50% of the effect (P

BackgroundVisceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn’s disease (CD); however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes.MethodsBody composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease–related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed.ResultsNinety-seven participants were assessed at baseline (55% male; median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to 3; P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3; 95% CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, –12; 95% CI, –19 to –4.5; P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL.ConclusionVAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution–dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD.

Inhibition of the heat shock protein 90 (Hsp90) chaperone is a promising therapeutic strategy to target expression of the androgen receptor (AR) and other oncogenic drivers in prostate cancer cells. However, identification of clinically-relevant responses and predictive biomarkers is essential to maximize efficacy and treatment personalization. Here, we combined mass spectrometry (MS)-based proteomic analyses with a unique patient-derived explant (PDE) model that retains the complex microenvironment of primary prostate tumors. Independent discovery and validation cohorts of PDEs (n = 16 and 30, respectively) were cultured in the absence or presence of Hsp90 inhibitors AUY922 or 17-AAG. PDEs were analyzed by LC-MS/MS with a hyper-reaction monitoring data independent acquisition (HRM-DIA) workflow, and differentially expressed proteins identified using repeated measure analysis of variance (ANOVA; raw p value

Objectives:Obstructive sleep apnoea (OSA) may be more common in people with schizophrenia compared to the general population, but the relative prevalence is unknown. Here, we determine the relative prevalence of severe OSA in a cohort of men with schizophrenia compared to representative general population controls, and investigate the contribution of age and body mass index (BMI) to differences in prevalence.Methods:Rates of severe OSA (apnoea–hypopnoea index > 30) were compared between male patients with schizophrenia and controls from a representative general population study of OSA.Results:The prevalence of severe OSA was 25% in the schizophrenia group and 12.3% in the general population group. In subgroups matched by age, the relative risk of severe OSA was 2.9 ( p = 0.05) in the schizophrenia subjects, but when adjusted for age and BMI, the relative risk dropped to 1.7 and became non-significant ( p = 0.17).Conclusions:OSA is prevalent in men with schizophrenia. Obesity may be an important contributing factor to the increased rate of OSA.

BACKGROUND Docetaxel is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC); however, many patients experience febrile neutropenia (FN) and cease treatment early due to toxicity. It is not known whether lower dose (LD) q3-weekly docetaxel impacts toxicity or efficacy. METHODS Multicenter retrospective study included 166 patients with mCRPC who received q3-weekly docetaxel between 2010 and 2015. Demographic, disease, chemotherapy (standard dose, SD > 60 mg/m2 vs LD ≤ 60 mg/m2 ) and toxicity data were collected. Univariable and multivariable logistic and competing risk regression models evaluated docetaxel-dose association with FN and early treatment cessation (ETC) due to toxicity. Associations between dose and efficacy end points were also evaluated. Analyses were repeated employing inverse propensity score weights. RESULTS Patients who received LD docetaxel (28.9%) were older with poorer Eastern Cooperative Oncology Group (ECOG) status. Fifteen percent of patients experienced FN, with a nonsignificant trend to lower incidence in the LD group (multiple adjusted odds ratio [OR] = 0.42; P = 0.21). Neither baseline patient nor prior treatment factors were predictive of FN. ETC due to toxicity occurred in 35%, with risk associated with increasing age, comorbidity count and poorer ECOG. There was no difference between LD and SD with respect to ETC due to toxicity, in unweighted and weighted analyses (LD vs SD, multivariable weighted hazard ratio [HR] = 1.47; P = 0.08). LD was associated with reduced prostate-specific antigen (PSA) response (50% vs 66.1%, multivariable weighted HR = 0.54; P = 0.03) and overall survival (median 7.9 vs 13.8 months, multivariable weighted HR = 2.19; P