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Metastasis‐directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5‐year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT‐based MDT. The primary endpoint was 5‐year treatment escalation‐free survival (TE‐FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone‐naïve at baseline. The rate of 5‐year TE‐FS was 21.7% (95% confidence interval [CI]: 15.7%–28.7%) overall and 25.4% (95% CI: 18.1%–33.9%) in the hormone‐naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4–5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05–2.01, p =.026), a higher baseline prostate‐specific antigen (PSA) (HR = 1.06, 95% CI: 1.03–1.09, p <.001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40–3.26, p <.001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow‐up, 18.9% (95% CI: 13.2%–25.7%) of participants were free from treatment escalation (median follow‐up of 67.9 months) and two participants had an undetectable PSA level. No treatment‐related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT‐based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT‐based MDT to standard‐of‐care ADT‐based approaches are required to evaluate the impact of delaying ADT on survival. [ABSTRACT FROM AUTHOR]

Background: Primary aldosteronism (PA) represents the most common and potentially curable cause of secondary hypertension. However, PA is not commonly screened for, and up to 34% of patients who screen positive do not complete the full diagnostic process. This suggests that the diagnostic process may pose a barrier to patients and may contribute to the under‐diagnosis of PA. Aims: To evaluate the willingness of the Australian general public to undergo testing for secondary causes of hypertension and identify enablers or barriers to testing from the patients' perspective. Methods: An online survey containing questions on knowledge and attitudes towards hypertension, willingness to be tested and enablers/barriers towards testing was distributed to the Australian community. Results: Of 520 adult respondents (mean age 50.4 years, SD 27.3 years; 28.8% hypertensive; 56.0% female), the majority of non‐hypertensive and hypertensive respondents (82.7% vs 70.0%; P = 0.03) were willing to undergo testing for a secondary cause of hypertension that involved blood and urine tests. Greater knowledge of hypertensive risk modification strategies and complications was predictive of willingness to be tested, whereas age, sex, education level, geographic location, socio‐economic status and cardiovascular comorbidities were not. The top three barriers to testing included fear of a serious underlying condition, lack of belief in further testing and increased stress associated with further testing. Conclusion: A high proportion of patients are willing to engage in testing for a secondary cause of hypertension. Education about the risks associated with hypertension and the testing process may overcome several barriers to testing. [ABSTRACT FROM AUTHOR]

Background Delayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT). Methods This randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time. Findings Between September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] -60 to -8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm. Conclusions In this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling. Trial registration This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897., Author(s): Tracey L. Sletten 1,2,*, Michelle Magee 1,2, Jade M. Murray 1,2, Christopher J. Gordon 2,3,4, Nicole Lovato 2,5, David J. Kennaway 6, Stella M. Gwini 7,8, Delwyn J. Bartlett [...]

Objectives: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia. Methods: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ≥ 60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome. Results: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001). Conclusions: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. Trial registration number: ACTRN12615001183572, 03/11/2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1–59.3%). The median length of treatment escalation‐free survival over the entire follow‐up period was 27.1 months (95% CI; 21.8–29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08–0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4–5 vs. 1–3 initial lesions. A prostate‐specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation. What's new? Metastasis‐directed therapy (MDT), involving surgery or stereotactic ablative radiotherapy, is a promising alternative treatment strategy for prostate cancer patients with metastatic disease. It remains unclear, however, which subsets of patients most benefit from MDT. Here, interim analysis of a large prospective trial involving fractionated stereotactic body radiotherapy (SBRT) for prostate cancer patients with up to five synchronous oligometastases shows that 2 years following SBRT, about half of patients did not require treatment escalation. In addition, nearly one‐quarter of patients had prostate‐specific antigen levels below baseline. The findings highlight the promise of SBRT for long‐term suppression of oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between the use of a flowchart incorporating Wells score, PERC rule and age‐adjusted D‐dimer and subsequent imaging and yield rates of computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion scans being ordered in the ED for the assessment of pulmonary embolism. Methods: A flowchart governing ED pulmonary embolism investigation was introduced across three EDs in Melbourne, Australia for a 12 month period. Comparison of pulmonary embolism imaging rates and yield with the preceding 12 months was performed. Results: A total of 1815 pre‐implementation scans were performed compared with 1116 scans post‐implementation. Because of growth in patient attendances over this time, this equated to an imaging rate of 14.5 per 1000 presentations pre‐implementation and 8.6 per 1000 presentations post‐implementation (P < 0.001). Overall pulmonary embolism imaging yield rates rose from 9.9% to 16.5% (P < 0.001). A total of 179 pre‐implementation pulmonary embolisms were identified, with an incidence of 1.4 per 1000 presentations. This compared to 184 pulmonary embolisms post‐implementation, with an incidence of 1.4 per 1000 presentations (P = 0.994). Conclusion: The introduction of a clinical flowchart incorporating Wells score, PERC rule and age‐adjusted D‐dimer was associated with an increase in ED computed tomography pulmonary angiogram and nuclear medicine ventilation perfusion yield rate from 9.9% to 16.5% across the three enrolment hospitals when investigating possible pulmonary embolism. This corresponded to a 40% relative reduction in pulmonary embolism imaging. Diagnosis rates remained unchanged and no cases of missed pulmonary embolism attributable to the flowchart were identified. [ABSTRACT FROM AUTHOR]

Key points: Approximately 5–10% pregnancies are affected by fetal growth restriction.Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia.The present study is the first to measure pulmonary artery thickness and stiffness.The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants.The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics. Bronchopulmonary dysplasia is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic pulmonary arteries. The present study aimed to characterize pulmonary artery mechanics and cardiac function in preterm infants with fetal growth restriction (FGR) compared to those appropriate for gestational age (AGA) in the early neonatal period. This prospective study reviewed 40 preterm infants between 28 to 32 weeks gestational age (GA). Twenty infants had a birthweight <10th centile and were compared with 20 preterm AGA infants. A single high resolution echocardiogram was performed to measure right pulmonary arterial and right ventricular (RV) indices. The GA and birthweight of FGR and AGA infants were 29.8 ± 1.3 vs. 30 ± 0.9 weeks (P = 0.78) and 923.4 g ± 168 vs. 1403 g ± 237 (P < 0.001), respectively. Assessments were made at 10.5 ± 1.3 days after birth. The FGR infants had significantly thicker right pulmonary artery inferior wall (843.5 ± 68 vs. 761 ± 40 μm, P < 0.001) with reduced pulsatility (51.6 ± 7.6 μm vs. 59.7 ± 7.5 μm, P = 0.001). The RV contractility [fractional area change (28.7 ± 3.8% vs 32.5 ± 3.1%, P = 0.001), tricuspid annular peak systolic excursion (TAPSE) (5.2 ± 0.3% vs. 5.9 ± 0.7%, P = 0.0002) and myocardial performance index (0.35 ± 0.03 vs. 0.28 ± 0.02, P < 0.001)] was significantly impaired in FGR infants. Significant correlation between RV longitudinal contractility (TAPSE) and time to peak velocity/RV ejection time (measure of RV afterload) was noted (r2 = 0.5, P < 0.001). Altered pulmonary vascular mechanics and cardiac performance reflect maladaptive changes in response to utero‐placental insufficiency. Whether managing pulmonary vascular disease will alter clinical outcomes remains to be studied prospectively. Key points: Approximately 5–10% pregnancies are affected by fetal growth restriction.Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia.The present study is the first to measure pulmonary artery thickness and stiffness.The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants.The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics. [ABSTRACT FROM AUTHOR]

Objectives Compensable injury increases the likelihood of having persistent pain after injury. Three-quarters of patients report chronic pain after traumatic injury, which is disabling for about one-third of patients. It is important to understand why these patients report disabling pain, in order to develop targeted preventative interventions. This study examined the experience of pain and disability, and investigated their sequential interrelationships with, catastrophising, kinesiophobia and self-efficacy 1 year after compensable and non-compensable injury. Design Observational registry-based cohort study. Setting Metropolitan Trauma Service in Melbourne, Victoria, Australia. Participants Participants were recruited from the Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry. 732 patients were referred to the study, 82 could not be contacted or were ineligible, 217 declined and 433 participated (66.6% response rate). Outcome measures The Brief Pain Inventory, Glasgow Outcome Scale, EuroQol Five Dimensions questionnaire, Pain Catastrophising Scale, Pain Self-Efficacy Questionnaire, Injustice Experience Questionnaire and the Tampa Scale of Kinesiophobia. Methods Direct and indirect relationships (via psychological appraisals of pain/injury) between baseline characteristics (compensation, fault and injury characteristics) and pain severity, pain interference, health status and disability were examined with ordinal, linear and logistic regression, and mediation analyses. Results Injury severity, compensable injury and external fault attribution were consistently associated with moderate-to-severe pain, higher pain interference, poorer health status and moderate-to-severe disability. The association between compensable injury, or external fault attribution, and disability and health outcomes was mediated via pain self-efficacy and perceived injustice. Conclusions Given that the associations between compensable injury, pain and disability was attributable to lower self-efficacy and higher perceptions of injustice, interventions targeting the psychological impacts of pain and injury may be especially necessary to improve longterm injury outcomes. [ABSTRACT FROM AUTHOR]