Differences in treatment choices for localised prostate cancer diagnosed in private and public health services.

OBJECTIVE: To compare treatments for localised prostate cancer for men diagnosed in private and public health services in Victoria. DESIGN: Retrospective analysis of Victorian Cancer Registry data linked to population-based administrative health datasets. SETTING, PARTICIPANTS: 29 325 Victorian men diagnosed with prostate cancer during 2011-2017. MAIN OUTCOME MEASURES: Proportions of men in private and public health services receiving radical prostatectomy (with or without curative radiation therapy) or curative external beam radiation therapy alone within 12 months of diagnosis. RESULTS: After adjusting for age, tumour classification and comorbidity, men diagnosed in private health services received radical treatment more frequently than men diagnosed in public health services (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.31-1.49). The proportion of private patients who underwent radical prostatectomy was larger than that for public patients (44% v 28%; OR, 2.28; 95% CI, 2.13-2.44) and the proportion of private patients who received curative external beam radiation therapy alone (excluding brachytherapy) was smaller (9% v 19%; OR, 0.45; 95% CI, 0.42-0.49). These differences were apparent for all International Society of Urological Pathology (ISUP) tumour grades. The magnitude of the difference for prostatectomy was greater for men aged 70 years or more; for radiation therapy alone, it was larger for those diagnosed before age 70. The differences between private and public services narrowed during 2011-2017 for men with ISUP grade 1 disease, but not ISUP grade 2-5 tumours. CONCLUSION: Prostate cancer treatment choices differ substantially between men diagnosed in private and public health services in Victoria. These differences are not explained by disease severity or comorbidity.

Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation.

UNLABELLED: Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S. PATIENTS: To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S. PATIENTS: Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S. PATIENTS: Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable across populations and can be explored as screening assays.

Characteristics of cancer diagnoses and staging in South Western Victoria: a rural perspective.

OBJECTIVE: Australian states and territories have legislation mandating reporting of cancer diagnoses; however, tumour stage at diagnosis, treatment plan and associated outcomes are not routinely recorded in cancer registries for all tumour types. This study describes the Evaluation of Cancer Outcomes study that collects detailed information for patients diagnosed with cancer in south-western Victoria. DESIGN: Retrospective data collection. SETTING: Population based. PARTICIPANTS: New cancer patients within the Barwon South Western region. MAIN OUTCOME MEASURES: Cancer incidence and staging data for a regional and rural area. RESULTS: In 2009, there were 1778 primary tumours. Prominent tumour streams included prostate, breast, colon, lung, lymphoma, melanoma and rectum. Stage at diagnosis was recorded for more than 50% of patients for the tumour streams of testis, breast, bowel, renal, lung, and head and neck. Patients reporting to health centres with an on-site oncologist as part of their team had a higher rate of staging recorded at diagnosis (48.0 versus 36.9%, P=0.01). More women (55.4%) than men (41.4%) had stage-recorded. CONCLUSION: The Evaluation of Cancer Outcomes study is an important initiative that collects information about newly diagnosed cases of cancer more detailed than is currently collected by the Cancer Council of Victoria. Future studies will build on this base dataset and provide valuable insight into the regional and rural experience of treatment pathways after diagnosis. More work is needed to bring more services to our rural patients, or more education is needed to encourage the recording of tumour staging.

Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti-TNF-refractory Crohn's disease.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting. AIM: To compare the effectiveness of ustekinumab and vedolizumab in anti-TNF-refractory Crohn's disease over 12 months. METHODS: Patients commencing ustekinumab or vedolizumab for anti-TNF-refractory Crohn's disease with minimum follow-up of 12 months were included. The primary outcome measure was the difference in steroid-free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid-free remission and clinical response and remission. RESULTS: We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid-free and clinical remission were significantly higher among ustekinumab-treated patients. After adjusting for confounders, steroid-free remission was higher among ustekinumab-treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06-7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89-4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007). CONCLUSIONS: Ustekinumab appeared more effective in treating anti-TNF-refractory Crohn's disease and more patients persisted with therapy.

Pregabalin in the Management of Painful Diabetic Neuropathy: A Narrative Review.

Pregabalin is a first-line treatment in all major international guidelines on the management of painful diabetic neuropathy (pDPN). Treatment with pregabalin leads to a clinically meaningful improvement in pain scores, offers consistent relief of pain and has an acceptable tolerance level. Despite its efficacy in relieving neuropathic pain, more robust methods and comprehensive studies are required to evaluate its effects in relation to co-morbid anxiety and sleep interference in pDPN. The sustained benefits of modulating pain have prompted further exploration of other potential target sites and the development of alternative GABAergic agents such as mirogabalin. This review evaluates the role of pregabalin in the management of pDPN as well as its potential adverse effects, such as somnolence and dizziness, which can lead to withdrawal in ~ 30% of long-term use. Recent concern about misuse and an increase in deaths linked to its use has led to demands for reclassification of pregabalin as a class C controlled substance in the UK. We believe these demands need to be tempered in relation to the difficulties it would create for repeat prescriptions for the many millions of patients with pDPN for whom pregabalin provides benefit.Plain Language Summary: Plain language summary available for this article.

Development of a multicentre automated model to reduce planning variability in radiotherapy of prostate cancer.

BACKGROUND AND PURPOSE: Inter-institutional studies highlighted correlation between consistent radiotherapy quality and improved overall patient survival. In treatment planning automation has the potential to address differences due to user-experience and training, promoting standardisation. The aim of this study was to evaluate implementation and clinical effect of a multicentre collaboratively-developed automated planning model for Intensity-Modulated Radiation Therapy/Volumetric-Modulated Arc Therapy of prostate. The model was built using a variety of public institutions' clinical plans, incorporating different contouring and dose protocols, aiming at minimising their variation. METHODS AND MATERIALS: A model using 110 clinically approved and treated prostate plans provided by different radiotherapy centres was built with RapidPlan (RP), for use on intact and post-prostatectomy prostate cases. The model was validated, distributed and introduced into clinical practice in all institutions. To investigate its impact a total of 126 patients, originally manually inverse planned (OP), were replanned using RP without additional planner manual intervention. Target and organ-at-risk (OAR) metrics were statistically compared between original and automated plans. RESULTS: For all centres combined and individually, RP provided plans comparable or superior to OP for all dose metrics. Statistically significant reductions with RP were found in bladder (V40Gy) and rectal (V50Gy) low doses (within 2.3% and 3.4% for combined and 4% and 10% individually). No clinically significant changes were seen for the PTV, independently of seminal vesicle inclusion. CONCLUSION: This project showed it is feasible to develop, share and implement RP models created with plans from different institutions treated with a variety of techniques and dose protocols, with the potential of improving treatment planning results and/or efficiency despite the original variability.

The Investigation and Treatment of Diabetic Gastroparesis.

PURPOSE: This review provides an update on the investigations and treatment options for gastroparesis. METHODS: A comprehensive literature search of Medline, PubMed, Embase and OVID was conducted which included all systematic reviews and research articles that focused on the diagnosis, investigations and management diabetic gastroparesis. FINDINGS: Dietary modifications and pharmacologic treatment with prokinetics to increase gastric motility form the mainstay of treatment. However, the use of prokinetics is limited by adverse effects and serious adverse effects, leaving metoclopramide as the only drug approved by the US Food and Drug Administration for the treatment of gastroparesis. Newer therapies, including motilin receptor agonists, ghrelin receptor agonists, and neurokinin receptor antagonists, are currently being investigated. Transpyloric stenting, gastric electrical stimulation, and gastric per-oral endoscopic myotomy provide mechanical options for intervention, and surgical interventions in severe intractable gastroparesis include laparoscopic pyloroplasty or gastrectomy. IMPLICATIONS: Advances to better understand the pathophysiology and management of diabetic gastroparesis have been limited, especially with discordance between symptoms and severity of delay in gastric emptying. Established treatment options are limited; however, recent pharmacologic and surgical interventions show promise.

Radiotherapy in the Barwon South Western Region: a rural perspective.

INTRODUCTION: Cancer-related mortality rates are higher in rural areas compared with urban regions. Whether there are corresponding geographical variations in radiotherapy utilisation rates (RURs) is the subject of this study. METHODS: RURs for the regional centre of Geelong and rural areas of the Barwon South Western Region were calculated using a population-based database (2009). RESULTS: Lower RURs were observed for rural patients compared with the Geelong region for prostate cancer (15.7% vs 25.8%, P = 0.02), rectal cancer (32.8% vs 44.7%, P = 0.11), lymphoma (9.4% vs 26.2%, P = 0.05), and all cancers overall (25.6% vs 28.9%, P = 0.06). This lower rate was significant in men (rural, 19.9%; Geelong, 28.3%; P = 0.00) but not in women (rural, 33.6%; Geelong, 29.7%; P = 0.88). Time from diagnosis to radiotherapy was not significantly different for patients from the two regions. Tumour staging within the rural and Geelong regions was not significantly different for the major tumour streams of rectal, prostate and lung cancer (P = 0.61, P = 0.79, P = 0.43, respectively). A higher proportion of tumours were unstaged or unstageable in the rural region for lung (44% vs 18%, P < 0.01) and prostate (73% vs 57%, P < 0.01) cancer. CONCLUSION: Lower RURs were observed in our rural region. Differences found within tumour streams and in men suggest a complexity of relationships that will require further study.

Can we reduce disease burden from osteoarthritis?

The comparison of disparate interventions for the prevention and management of osteoarthritis (OA) is limited by the quality and quantity of published efficacy studies and the use of disparate measures for reporting clinical trial outcomes. The "transfer to utility" technique was used to translate published trial outcomes into a health-related quality-of-life (utility) scale, creating a common metric which supported comparisons between disparate interventions. Total hip replacement (THR) and total knee replacement (TKR) surgery were the most effective treatments and also highly cost-effective, at estimated cost per quality-adjusted life-year (QALY) of 7500 dollars for THR and 10000 dollars for TKR (best estimate). Other apparently highly cost-effective interventions were exercise and strength training for knee OA (< 5000 dollars/QALY), knee bracing, and use of capsaicin or glucosamine sulfate (< 10000 dollars/QALY). The cost per QALY estimates of non-specific and COX-2 inhibitor non-steroidal anti-inflammatory drugs were affected by treatment-related deaths and highly sensitive to the discounting of life-years lost. OA interventions that have been shown to be ineffective (eg, arthroscopy) are targets for redistribution of healthcare resources. OA interventions which lack efficacy studies (eg, prevention programs) require further research to assist priority setting. The application of the Health-sector Wide model to OA demonstrates its role as an evidence-based model that can be successfully applied to identify marginal interventions - those to be expanded and contracted to reduce the expected burden of disease, within current healthcare resources.