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PurposeThe purpose of this study is to determine if there is an additive effect of combined advanced maternal and paternal age on pregnancy and live birth rates.MethodsRetrospective data analysis of 4057 first cycles at a fertility centre between 2009 and 2013 was compiled. Donor, preimplantation genetic screening and double embryo transfer cycles were excluded. Main outcomes measured were clinical pregnancy, viable pregnancy, live birth and term birth.ResultsLogistic regression indicated strong negative associations for maternal ages exceeding 27 years with clinical pregnancies (p < 0.001), viable pregnancies (p < 0.001), live births (p < 0.001) and term births (p < 0.001). There was evidence of negative associations between paternal age and both viable pregnancies (p = 0.06) and live births (p = 0.04), such that the probability of pregnancy was 10% further reduced for women who were 35 years with a partner over 40 years vs. women aged 35 years with a partner under 30 years. There was evidence of an interaction between maternal age and the paternal age on term births (p = 0.02) such that advanced paternal age’s effect on the probability of a term birth was only evident in couples where the maternal age ranged between ~27 and 35 years.ConclusionsThere is an additive effect to pregnancy and live birth rates when both partners are of an advanced age, thus highlighting the need for pre-conception public health messaging and a combined approach to ART counselling assessing both parental ages in combination.

While psychotherapeutic e-mental health interventions may circumvent barriers that many men face in accessing mental health care, the effects of men using these interventions have not been evaluated. We aimed to synthesise the characteristics of psychotherapeutic e-mental health interventions for depression or anxiety that have been trialled and evaluated in men, and synthesise and meta-analyse the effects of these interventions on men’s depression and anxiety, including examining influences of participant, intervention, and study characteristics on outcomes. Seven papers ( N  = 552 participant men) identified from systematic literature searches met inclusion criteria. A total 177 studies were excluded because although they met all other inclusion criteria, they did not present analysable data on participant men. The seven included interventions varied in content, length, and format; only one intervention was gender sensitive, having been designed specifically for men. All three randomised controlled trials detected no post-trial difference in men’s depression symptoms between intervention and 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 two studies, which found a medium-sized, positive effect of depression treatment interventions on depression symptoms in pre-post data ( g  = 0.64, p  < 0.005). Further meta-analyses could not be conducted due to data limitations. Psychotherapeutic e-mental health treatment interventions result in pre- to post-intervention improvements in men’s depression symptoms. There is urgent need for consideration of gender and sex in the development, evaluation, and dissemination of e-mental health interventions for men, and for further information on their effects.

Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35-80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (β = 0.409, p<0.001), TT (β = 0.560, p<0.001), fT4 (β = 0.067, p = 0.019) and SHBG, and negative associations between triglycerides (β = -0.112, p<0.001), abdominal fat mass (β = -0.068, p = 0.032) and E2 (β = -0.058, p = 0.050) and SHBG. In longitudinal analysis the positive determinants of SHBG at 4.9 years were age (β = 0.406, p = <0.001), TT (β = 0.461, p = <0.001), and fT4 (β = 0.040, p = 0.034) and negative determinants were triglycerides (β = -0.065, p = 0.027) and abdominal fat mass (β = -0.078, p = 0.032). Taken together these data suggest low SHBG is a marker of abdominal obesity and increased serum triglycerides, conditions which are known to have been associated with low testosterone and low T4.

Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes. In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment. Patients were randomly assigned (in a 1:1 ratio, stratified by previous first-line chemotherapy, histological subtype, and recruiting hospital) to receive thalidomide 200 mg per day (including a 2 week run in of 100 mg per day) plus active supportive care or active supportive care alone until disease progression. Patients were required to be registered and to start treatment with thalidomide within 10 weeks after the end of the first-line chemotherapy. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity. The primary endpoint was time to progression. The primary analyses were by intention to treat. The study is registered, ISRCTN13632914. Between May 11, 2004, and Dec 23, 2009, we randomly assigned 222 patients, 111 in each group (one patient on active supportive care later withdrew consent and was excluded from analyses). At the time of this final analysis, median follow-up was 33·1 months (IQR 22·3–66·8), and physician-reported disease progression had occurred in 104 patients in the thalidomide group and 107 in the active supportive care group; 92 patients in the thalidomide group and 93 in the active supportive care group had died. Median time to progression in the thalidomide group was 3·6 months (95% CI 3·2–4·1) compared with 3·5 months (2·3–4·8) in the active supportive care group (hazard ratio 0·95, 95% CI 0·73–1·20, p=0·72). 43 (39%) grade 3 or 4 adverse events were reported in the thalidomide group and 31 (28%) in the active supportive care group; neurosensory events were reported by two (2%) patients on thalidomide and none on active supportive care, cardiac events by two (2%) patients on thalidomide and three (3%) on active supportive care, and thromboembolic events by three (3%) patients on thalidomide and none on active supportive care. No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma. Dutch Cancer Society (KWF), Eli Lilly, NSW Dust Disease Compensation Board, University of Sydney, and Cancer Australia.

Background In 2020, a research group published five linear longitudinal models, predict Expanded Prostate Cancer Index Composite-26 (EPIC-26) scores post-treatment for radical prostatectomy, external beam radiotherapy and active surveillance collectively in US patients with localized prostate cancer. Methods Our study externally validates the five prediction models for patient reported outcomes post-surgery for localised prostate cancer. The models’ calibration, fit, variance explained and discrimination (concordance-indices) were assessed. Two Australian validation cohorts 1 and 2 years post-prostatectomy were constructed, consisting of 669 and 439 subjects, respectively (750 in total). Patient reported function in five domains post-prostatectomy: sexual, bowel, hormonal, urinary incontinence and other urinary dysfunction (irritation/obstruction). Domain function was assessed using the EPIC-26 questionnaire. Results 1 year post-surgery, R 2 was highest for the sexual domain (35%, SD = 0.02), lower for the bowel (21%, SD = 0.03) and hormone (15%, SD = 0.03) domains, and close to zero for urinary incontinence (1%, SD = 0.01) and irritation/obstruction (− 5%, SD = 0.04). Calibration slopes for these five models were 1.04 (SD = 0.04), 0.84 (SD = 0.06), 0.85 (SD = 0.06), 1.16 (SD = 0.13) and 0.45 (SD = 0.04), respectively. Calibration-in-the-large values were − 2.2 (SD = 0.6), 2.1 (SD = 0.01), 5.1 (SD = 0.1), 9.6 (SD = 0.9) and 4.0 (SD = 0.2), respectively. Concordance-indices were 0.73, 0.70, 0.70, 0.58 and 0.62, respectively (all had SD = 0.01). Mean absolute error and root mean square error were similar across the validation and development cohorts. The validation measures were largely similar at 2 years post-surgery. Conclusions The sexual, bowel and hormone domain models validated well and show promise for accurately predicting patient reported outcomes in a non-US surgical population. The urinary domain models validated poorly and may require recalibration or revision.

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.

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 Redesigning primary health services may enhance timely and effective uptake by men. The primary aim of this study was to assess the likelihood of Australian men attending a dedicated men’s health service (DMHS). The further aims were to better understand the reasons for their preferences and determine how health behaviours influence likelihood. Methods A survey on health service use and preferences, health help-seeking behaviours, and the likelihood of attending a DMHS was administered by telephone to 1506 randomly selected men (median age 56 years, range 19–95). Likelihood of attending a DMHS was rated using a single item Likert scale where 0 was not at all likely and 10 highly likely. Respondents were classified by age (< or > = 65 years) and health status. Principal component analyses were used to define health behaviours, specifically help-seeking and delay/avoidance regarding visiting a doctor. Multivariable linear and logistic regression analyses were used to examine predictors of likelihood of attending a DMHS. Results The mean likelihood of attending a DMHS was 5.8 (SD 3.3, median 6, moderate likelihood) and 21%, 26% and 23% of men rated likelihood as moderate, high and very high respectively. Being happy with their existing doctor was the most common reason (52%) for being less likely to attend a DMHS. In unadjusted analyses, younger men reported being more likely to attend a DMHS ( p  < 0.001) with older-sick men reporting being least likely ( p  < 0.001). Younger men were more likely than older men to score higher on delay/avoidance and were more likely to self-monitor. In the full model, men with current health concerns ( p  ≤ 0.01), who scored higher on delay/avoidance ( p  ≤ 0.0006), who were more likely to be information-seekers ( p  < 0.0001) and/or were motivated to change their health ( p  ≤ 0.0001) reported a higher likelihood of attending a DMHS irrespective of age and health status. Conclusions Seventy percent of men reported a moderate or higher likelihood of attending a DMHS. As young healthy men are more likely than older men to display health behaviours that are associated with a higher likelihood of attending a DHMS, such as delay/avoidance, marketing a DMHS to such men may be of value.

Farming is physically and psychologically hazardous. Farmers face many barriers to help seeking from traditional physical and mental health services; however, improved internet access now provides promising avenues for offering support. This study aims to co-design with farmers the content and functionality of a website that helps them adopt transferable coping strategies and test its acceptability in the broader farming population. Research evidence and expert opinions were synthesized to inform key design principles. A total of 18 farmers detailed what they would like from this type of website. Intervention logic and relevant evidence-based strategies were mapped. Website content was drafted and reviewed by 2 independent mental health professionals. A total of 9 farmers provided detailed qualitative feedback on the face validity of the draft content. Subsequently, 9 farmers provided feedback on the website prototype. Following amendments and internal prototype testing and optimization, prototype usability (ie, completion rate) was examined with 157 registered website users who were (105/157, 66.9%) female, aged 21-73 years; 95.5% (149/156) residing in inner regional to very remote Australia, and 68.2% (107/157) \"sheep, cattle and/or grain farmers.\" Acceptability was examined with a subset of 114 users who rated at least module 1. Interviews with 108 farmers who did not complete all 5 modules helped determine why, and detailed interviews were conducted with 18 purposively sampled users. Updates were then made according to adaptive trial design methodology. This systematic co-design process resulted in a web-based resource based on acceptance and commitment therapy and designed to overcome barriers to engagement with traditional mental health and well-being strategies-ifarmwell. It was considered an accessible and confidential source of practical and relevant farmer-focused self-help strategies. These strategies were delivered via 5 interactive modules that include written, drawn, and audio- and video-based psychoeducation and exercises, as well as farming-related jokes, metaphors, examples, and imagery. Module 1 included distress screening and information on how to speak to general practitioners about mental health-related concerns (including a personalized conversation script). Modules were completed fortnightly. SMS text messages offered personalized support and reminders. Qualitative interviews and star ratings demonstrated high module acceptability (average 4.06/5 rating) and suggested that additional reminders, higher quality audio recordings, and shorter modules would be useful. Approximately 37.1% (52/140) of users who started module 1 completed all modules, with too busy or not got to it yet being the main reason for non-completion, and previous module acceptability not predicting subsequent module completion. Sequential integration of research evidence, expert knowledge, and farmers' preferences in the co-design process allowed for the development of a self-help intervention that focused on important intervention targets and was acceptable to this difficult-to-engage group. Australian New Zealand Clinical Trials Registry ACTRN12617000506392; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372526.

Background Dyspnea is the most common symptom in patients with malignant pleural effusion (MPE). Treatment decisions are primarily based on the perception of dyspnea severity. Aims To study dyspnea perception following therapeutic thoracentesis using the visual analog scale (VAS) dyspnea score and modified Borg scale (MBS). To investigate whether patient reported outcome (PRO) measures can predict pleural re-interventions. Patients and methods Consecutive patients presenting with symptomatic MPE and planned for therapeutic thoracentesis were asked to complete MBS and VAS dyspnea scores (both at rest and during exercise) daily for 14 consecutive days. Physicians, unaware of the results of these PRO measures, decided on the necessity of a re-intervention, according to routine care. PRO measures were analyzed and correlated with performed re-interventions and the volume of removed fluid. Results Forty-nine out of 64 consecutive patients returned the diaries. Twenty-eight patients (57 %) had a re-intervention within 30 days. Patients who required a re-intervention reported significantly higher MBS than patients who did not. The extent of increase in MBS during exercise was related to the need for re-intervention. Regarding the MBS during exercise, median time to maximal relief was 2 days. Re-intervention was required sooner when larger volumes were drained. Conclusion Patient reported outcomes are useful tools to assess treatment effect of therapeutic thoracentesis. Median time to maximal relief is 2 days. MBS rather than VAS dyspnea score appears to be more prognostic for repeat pleural drainage within 30 days.