5-alpha reductase inhibitors use in prostatic disease and beyond.

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

Increased burden on metropolitan urological services: The era of the Australian National Emergency Access Targets (NEAT or the "4-h target").

BACKGROUND: The National Emergency Access Targets (NEAT) was introduced in Australia in 2011 and guides the clearance of presentations within 4-h of initial presentation from the Emergency Department (ED). We aim to assess the impact of the introduction of NEAT on acute urological services at a large metropolitan center. METHODS: A retrospective cohort study was performed and data were collected from electronic patient management systems. The control group was represented by ED presentations between June and September 2011, 1 year prior to the introduction of NEAT. The two study groups consisted of ED presentations between June and September 2012 and 2013, respectively. Outcome measures included time to the ureteric stent and scrotal exploration, inpatient length of stay (IPLOS), out-of-hours operating, and hospital mortality rates. RESULTS: Across the three study periods, a total of 76,935 patients were assessed by the EDs of the health service. 225 urological inpatient episodes were included across all periods with a trend showing increasing numbers of admissions (P = 0.003). For patients admitted under the urological service: Waiting room time and ED length of stay decreased significantly (P < 0.001). Proportion of operative cases decreased insignificantly (P = 0.275). Time from emergency presentation to emergency ureteric stent remained unchanged, however, proportions of procedures performed out-of-hours showed an increasing trend (P < 0.001). A significant increase in inter-unit transfer was observed, however, median IPLOS and mortality for operative and nonoperative cases remain unchanged. CONCLUSIONS: Concerning urological admissions, the implementation of NEAT has been associated with improvement in ED key performance indicators. Such changes have been correlated with reductions in operative cases and increases in out-of-hours emergency operating. Further research is required to evaluate the direct effect of NEAT on urological patient care.

The 'four-hour target' and the impact on Australian metropolitan acute surgical services.

BACKGROUND: The National Emergency Access Targets (NEAT), introduced in 2012, guides the clearance of emergency department (ED) presentations within 4 h of initial presentation. We aim to assess the impact of NEAT on acute surgical services at a large metropolitan centre. METHODS: A retrospective cohort study was performed and data were collected from electronic patient management systems. The control group was represented by ED presentations between June and September 2011, 1 year prior to the introduction of NEAT. The two study groups consisted of ED presentations between June and September 2012 and 2013 respectively. Outcome measures included time to appendicectomy and cholecystectomy, inpatient length of stay (IPLOS) (for operative and non-operative cases), out-of-hours operating and hospital mortality rates. RESULTS: In total, 2619 inpatient episodes were included, with a trend showing increasing admissions throughout the study periods (P < 0.001). Time to surgical review and ED length of stay decreased significantly (P < 0.001). Time from emergency presentation to emergency appendicectomy and cholecystectomy remained unchanged and procedures performed out-of-hours increased significantly from 20.9% to 42.9% (P < 0.001). Median IPLOS for operative and non-operative patients was reduced during the study from 2.05 to 1.84 days (P < 0.001). Inter-unit transfers within 48 h of presentation increased significantly from 5.3% to 14.7% (P < 0.001). CONCLUSIONS: The early results following the implementation of NEAT have been correlated with increased efficiency in ED clearance and increased burden on surgical operative and inpatient outcomes. While improvements in IPLOS were observed, they must be considered in the context of increased lower-acuity admissions and out-of-hours operating.

Clearing emergency departments and clogging wards: National Emergency Access Target and the law of unintended consequences.

OBJECTIVE: To assess ED length of stay (EDLOS), access block, inpatient length of stay (IPLOS) and waiting times before and after the implementation of the National Emergency Access Target (NEAT). METHODS: This was designed as a retrospective cohort study and data was collected from electronic patient management systems. The control group represented all emergency presentations between June 2011 and September 2011, 1 year prior to the introduction of NEAT. The study groups were assessed and included all ED presentations between June and September 2012 and 2013 respectively. Main outcome measures were waiting times, EDLOS, proportion of patients cleared from the ED within NEAT goals, hospital length of stay and hospital mortality rates. RESULTS: A cumulative total of 76 935 patients were included in the study. During the course of the study, clearance from the ED within NEAT targets rose from 49.0% to 53.2% [relative risk (RR) 1.09; 95% CI, 1.07-1.11; P < 0.001]. ED waiting times decreased from 1.05 h [interquartile range (IQR), 0.43-2.27] to 0.45 h (IQR, 0.17-1.22) (P < 0.001) and time from bed-request to ward access increased. Utilisation of emergency short stay units (SSU) increased significantly across the study period from 6.5% to 13.4% (P < 0.001). Rates of inpatient transfers increased eightfold (RR, 7.93; 95% CI, 5.98-10.51; P < 0.001) and IPLOS increased by 21% from 2.05 (IQR, 0.75-4.96) to 2.50 days (IQR, 1.12-4.99) (P < 0.001). Hospital mortality remained unchanged from 3.0% to 3.3% (RR, 1.10; 95% CI, 0.91-1.34; P = 0.311). CONCLUSIONS: At the current institution NEAT success has been guarded, likely secondary to availability of inpatient beds. The implementation of NEAT appears to have reduced emergency waiting times. These early results suggest concurrent a detrimental effect on IPLOS; however, some of this effect may be a result of a large increase in short stay admissions.