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We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16–4.51) and lung (aSHR, 1.93; 95%CI 1.05–3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding.

Men living in regional and remote areas experience disparities in prostate cancer (PrCa) diagnosis, clinical characteristics and treatment modalities. We sought to determine whether such disparities exist in PrCa patients from Tasmania; a regional state of Australia with the second-highest rate of diagnosis and where over a third of residents live in outer regional and remote areas. Our study included clinicopathological data from 1526 patients enrolled in the Prostate Cancer Outcomes Registry-Tasmania. Regression analyses were undertaken to determine whether demographic, clinical and treatment variables differed between inner regional and outer regional/remote patients. Men from outer regional/remote areas were significantly more likely to reside in lower socio-economic areas, be diagnosed at a later age and with more clinically aggressive features. However, in contrast to previous studies, there were no overall differences in diagnostic or treatment method, although men from outer regional/remote areas took longer to commence active treatment and travelled further to do so. This study is the first to investigate PrCa disparities in a wholly regional Australian state and highlights the need to develop systematic interventions at the patient and healthcare level to improve outcomes in outer regional and remote populations in Australia and across the globe.

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p  < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (n paired  = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; n paired  = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB ). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.

Background and Purpose Evidence on how treatment outcomes vary by patient characteristics helps to inform clinical practice. In this study, we measured socioeconomic and geographic disparity in post‐radiotherapy procedures, as an indication of short‐term radiotherapy adverse effects, among men with prostate cancer. Materials and Methods We studied 8344 South Australian diagnosed men with prostate cancer (2002–2020) who received external beam radiotherapy. The outcomes were anorectal and urinary procedures, identified using hospital admission procedure codes and Medicare Benefits Schedule item codes. Crude rates per 1000 person‐time were estimated at two years post‐radiotherapy. Socioeconomic and geographic disparities were identified through multivariable adjusted zero‐inflated Poisson regression. Results Fifteen percent of men underwent at least one post‐radiotherapy procedure within two years. The rates of anorectal, urinary and overall (both anorectal and urinary) procedures were 18, 66 and 81 per 1000 person‐years, respectively. Men in the highest socioeconomic quintile had lower rates of overall (incidence rate ratio [IRR] 0.70, 95% CI: 0.61–0.81), anorectal (IRR 0.32, 95% CI: 0.20–0.52) and urinary (IRR 0.69, 95% CI: 0.56–0.86) procedures than men in the lowest socioeconomic quintile. Men from non‐metropolitan areas had higher rates of anorectal procedures (IRR 1.36, 95% CI: 1.05–1.77) than men from metropolitan areas, which was further compounded by low socioeconomic advantage. Receiving radiotherapy in more recent years was associated with lower rates of post‐radiotherapy procedures. Conclusion Anorectal and urinary procedures following radiotherapy significantly vary across different population subgroups. Observed differences in procedure rates may suggest socioeconomic and geographic disparities in radiotherapy adverse effects for prostate cancer. This underscores the importance of follow‐up care for at‐risk population subgroups.

Background Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the standard of care for diabetic macular edema (DME), a common complication of diabetes. This study aimed to identify factors influencing DME intravitreal anti-VEGF treatment outcomes in real-world practice. Methods This was a multi-center retrospective observational study using medical chart review of participants receiving anti-VEGF injections for DME (N = 248). Demographic and clinical variables were assessed for association with best corrected visual acuity (BCVA) and central macular thickness (CMT) outcomes using regression models. Results There was a significant improvement in BCVA (p < 0.001) and CMT (p < 0.001) after 12 months of treatment, although 21% of participants had decreased BCVA, and 41% had a < 10% CMT reduction at 12 months. Higher baseline BCVA (p = 0.022, OR=-0.024, 95% CI=-0.046,-0.004) and longer duration of diabetic retinopathy (p = 0.048, OR=-0.064, 95% CI=-0.129,-0.001) were negative predictors for BCVA response, whereas Aflibercept treatment (p = 0.017, OR = 1.107, 95% CI = 0.220,2.051) compared with other drugs and a positive “early functional response” (p < 0.001, OR=-1.393, 95% CI=-1.946,-0.857) were positive predictors. A higher baseline CMT (p < 0.001, OR = 0.019, 95% CI = 0.012,0.0261) and an “early anatomical response”, (p < 0.001, OR=-1.677, 95% CI=-2.456, -0.943) were predictors for greater reduction in CMT. Overall, the variables could predict only 23% of BCVA and 52% of CMT response. Conclusions The study shows a significant proportion of DME patients do not respond to anti-VEGF therapy and identifies several clinical predictors for treatment outcomes. Trial registration The study was approved through the Human Research Ethics Committee, University of Tasmania (approval number H0012902), and the Southern Adelaide Clinical Human Research Ethics Committee (approval number 86 − 067).

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). DR is complex and the term encompasses several clinical subtypes of diabetic eye disease, including diabetic macular edema (DME), the most frequent cause of central vision loss in DR patients. Both genetic and environmental factors contribute to the pathophysiology of DR and its subtypes. While numerous studies have identified several susceptibility genes for DR, few have investigated the impact of genetics on DME susceptibility. This review will focus on the current literature surrounding genetic risk factors associated with DME. We will also highlight the small number of studies investigating the genetics of response to antivascular endothelial growth factor (anti-VEGF) injection, which is used to treat DME.

Objectives To assess whether insulin therapy impacts the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of diabetic macular edema (DME) in type 2 diabetes mellitus. Methods This was a retrospective multi-center analysis. The best-corrected visual acuity (BCVA) at 12 months, BCVA change, central macular thickness (CMT), CMT change, and cumulative injection number were compared between the insulin and the oral hypoglycemic agent (OHA) groups. Results The mean final BCVA and CMT improved in both the insulin ( N  = 137; p  < 0.001; p  < 0.001, respectively) and the OHA group ( N  = 61; p  = 0.199; p  < 0.001, respectively). The two treatment groups were comparable for final BCVA ( p  = 0.263), BCVA change ( p  = 0.184), final CMT ( p  = 0.741), CMT change ( p  = 0.458), and the cumulative injections received ( p  = 0.594). The results were comparable between the two groups when stratified by baseline vision ( p  > 0.05) and baseline HbA1c ( p  > 0.05). Conclusion Insulin therapy does not alter treatment outcomes for anti-VEGF therapy in DME.

Drug prescription registries has become an alternative data source to hospital admission databases for measuring comorbidities. However, the predictive validity of prescription-based comorbidity measures varies based on the population under investigation and outcome of interest. We aimed to determine which prescription-based index of comorbidity has most utility in Australian men with prostate cancer. We studied 25,414 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked datasets. The Rx-Risk index, Chronic Disease Score (CDS), Drug Comorbidity Index (DCI) and Pharmaceutical Prescribing Profile (P3) with one year lookback period from prostate cancer diagnosis were evaluated. The predictive ability of each index to determine all-cause deaths within two and five years of prostate cancer diagnosis was compared using the c-statistic from flexible parametric survival models, adjusting for age, socioeconomic status and year of prostate cancer diagnosis. The Rx-Risk index performed better in predicting two-year (c-statistic = 0.818) and five-year (c-statistic = 0.784) all-cause mortality than P3, CDS and DCI. Including comorbidity measures as continuous scores resulted in a better performance than including them as categories. Grouping scores into four categories (≤0, >0 - ≤1, >1 - ≤2, and >2) resulted in better performance and calibration than using fewer categories. Rx-Risk was validated in Australia and reflects Australian prescribing patterns. It showed better predictive performance for mortality in our study, with a modest improvement over P3, CDS and DCI. For research with prostate cancer populations, we recommend the use of drug-based comorbidity indices that have been validated in a similar population. •All the four drug-based comorbidity indices have utility in predicting mortality.•Rx-Risk index performed better in our study cohort.•Rx-Risk was validated in Australia and reflects Australian prescribing patterns.•The findings suggest using drug-based indices validated in a similar setting.

To compare the utility of various admission-based comorbidity indices in men diagnosed with non-metastatic prostate cancer. The study cohort consisted of men diagnosed with prostate cancer between January 2002 and December 2020 according to the state-wide South Australian Cancer Registry. Comorbid conditions were captured for 11,470 men through linkage to public hospital admission data 5-years prior to prostate cancer diagnosis. The comorbidity indices evaluated included the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), National Cancer Institute (NCI) comorbidity index, and Cancer, Care and Comorbidity (C3) index. The predictive performance of the four indices for 5-year overall mortality was compared using the C-statistic from Cox proportional hazard models adjusted for age, socioeconomic status, and year of prostate cancer diagnosis. Approximately 31 %, 45 %, 28 % and 47 % of patients had at least one comorbid condition captured by CCI, ECI, NCI and C3, respectively. Regarding the prediction of 5-year overall survival, CCI (c-index = 0.763) slightly higher predictive performance than ECI (0.758), NCI (0.755), and C3 (0.754). Indices in their continuous score resulted in better predictive performance than them being used categorically (0, 1, and 2 +). The NCI (continuous score) showed a stronger association with overall mortality (hazard ratio (HR) 2.47, 95%CI:2.29–2.67) than the other indices, despite its predictive performance being lower than the CCI and ECI. There were only slight differences in the predictive accuracy among the indices, with the CCI having a slightly better prognostic value than the other indices. All four indices demonstrated a strong association with mortality in men diagnosed with prostate cancer. •The prognostic value of the four comorbidity indices varied only slightly.•Indices have better predictive performance when used as continuous scores.•NCI showed strong association with mortality but lower predictive performance.•The distribution of comorbidity scores differs substantially between indices.

ObjectiveTo compare the visual outcomes of intravitreal antivascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in a real-world setting.Methods and analysisRetrospective analysis of data from the Tasmanian Ophthalmic Biobank database. The median change in best-corrected visual acuity (BCVA) between baseline and 12 months post initiating intravitreal anti-VEGF treatment were compared between the three diseases. Final BCVA, central macular thickness (CMT), cumulative number of injections and overall predictors of change in BCVA and CMT were also determined.ResultsAt 12 months, change in BCVA was significantly different between nAMD, DMO and RVO cohorts (p=0.032), with lower median change for DMO (2 letters, range −5 to 20) than for RVO (11 letters, range −20 to 35). Likewise, CMT change was significantly different between the three cohorts (p=0.022), with a smaller reduction in CMT in DMO (−54 µm, range −482 to 50) than RVO patients (−137 µm, range −478 to 43; p=0.033). Total number of injections received (p=0.028) and final BCVA score (p=0.024) were also significantly different between the groups. Baseline BCVA was a negative predictor (p=0.042) and baseline CMT a positive predictor (p<0.001) of outcome. After adjusting for baseline BCVA and CMT, diagnosis of nAMD or RVO was a predictor of visual improvement compared with the DMO.ConclusionsAt the end of 12 months, nAMD and RVO cohorts had the greatest improvement in BCVA, however the final BCVA for DMO was significantly better than for nAMD.