Rates of diabetic retinopathy screening in pregnant patients with type 1 and type 2 diabetes in a predominantly Indigenous Central Australian population.

BACKGROUND: Pregnancy is a risk factor for the progression of diabetic retinopathy (DR) in women with pre-gestational diabetes. Australian screening guidelines recommend DR screening in the first trimester of pregnancy. The rates of DR screening in pregnant patients with pre-gestational diabetes are unknown in Australia. AIM: To determine the rates of DR screening in pregnant women with pre-gestational diabetes at Alice Springs Hospital Diabetes Antenatal Care and Education (DANCE) clinic. MATERIALS AND METHODS: Retrospective review of women with pre-gestational diabetes who attended the DANCE clinic between July 2016 and June 2020. RESULTS: There were 146 pregnancies in 144 individual women included in this review. There were 93% (n = 134) who identified as Aboriginal but not Torres Strait Islander. DR screening was performed in 23 (16%) pregnancies, in which DR was present in six (26%) and no retinal abnormality was found in 17 (74%). Of seven (5%) women who had a history of DR, only three had a screen during the pregnancy period. The location of the DR screen included Alice Springs Hospital (17%, n = 4), Alice Springs general practice clinics (35%, n = 8) and remote NT community clinics outside of Alice Springs (39%, n = 9). The trimesters in which women received their DR screens were: trimester 1, 45%, n = 10; trimester 2, 39%, n = 9; trimester 3, 17%, n = 4. CONCLUSION: The minority of pregnant women who attend the DANCE clinic at Alice Springs Hospital received DR screening in adherence with national guidelines.

Frequent Subgraph Mining of Functional Interaction Patterns Across Multiple Cancers.

Molecular mechanisms characterizing cancer development and progression are complex and process through thousands of interacting elements in the cell. Understanding the underlying structure of interactions requires the integration of cellular networks with extensive combinations of dysregulation patterns. Recent pan-cancer studies focused on identifying common dysregulation patterns in a confined set of pathways or targeting a manually curated set of genes. However, the complex nature of the disease presents a challenge for finding pathways that would constitute a basis for tumor progression and requires evaluation of subnetworks with functional interactions. Uncovering these relationships is critical for translational medicine and the identification of future therapeutics. We present a frequent subgraph mining algorithm to find functional dysregulation patterns across the cancer spectrum. We mined frequent subgraphs coupled with biased random walks utilizing genomic alterations, gene expression profiles, and protein-protein interaction networks. In this unsupervised approach, we have recovered expert-curated pathways previously reported for explaining the underlying biology of cancer progression in multiple cancer types. Furthermore, we have clustered the genes identified in the frequent subgraphs into highly connected networks using a greedy approach and evaluated biological significance through pathway enrichment analysis. Gene clusters further elaborated on the inherent heterogeneity of cancer samples by both suggesting specific mechanisms for cancer type and common dysregulation patterns across different cancer types. Survival analysis of sample level clusters also revealed significant differences among cancer types (p < 0.001). These results could extend the current understanding of disease etiology by identifying biologically relevant interactions.Supplementary Information: Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/FSM_Pancancer.

Updating the model of eye care for Aboriginal populations in remote Central Australia.

Eye disease is the third-highest contributor towards health inequality for Aboriginal Australians. Understanding how the Central Australian ophthalmology service addresses complexities of remote eye care is crucial in understanding how expansion can meet current and future needs. The present study analyses findings from the MEDLINE database and Governmental reports, and descriptive information from stakeholders in Central Australia and the Australian Department of Health. We describe the current Central Australian ophthalmology model at three levels; (a) the healthcare service level (specialized primary care, local/outreach optometry and ophthalmology services, and intensive extended surgical weeks), (b) the community level (local community staff, clinics and initiatives, and eye "champions" and mutual support), and (c) the healthcare system level (federal and state government, and private funding). We conclude that building full-time specialist availability, and system-wide approaches to increase patient utilisation, will facilitate overcoming barriers of remoteness, and create enduring improvements in Central Australian eye care and health-inequality.

Visual Outcomes in the Management of Diabetic Maculopathy in Central Australia.

PURPOSE: In major urban centres and high-resource settings, treatment of diabetic maculopathy with anti-Vascular Endothelial Growth Factor (VEGF) injections has largely displaced laser treatment. However, intravitreal therapy alone requires frequent follow-up, a barrier to adherence in remote Australia. We report vision outcomes of phased diabetic maculopathy treatment in remote Central Australia for maculopathy using laser and, in a subset, supplementary injection treatment. METHODS: We audited clinical records of patients undergoing laser treatment for diabetic maculopathy between 2001 and 2013 at an ophthalmology service based at Alice Springs Hospital, a regional hub in remote Australia. All patients receiving macular laser treatment were included, and some required supplementary injection(s). The primary outcome measure was change in best-corrected visual acuity [BCVA] from baseline treatment. RESULTS: Of 338 maculopathy-treated patients, 88% were indigenous and 39% were male. Of 554 maculopathy laser-treated eyes, 118 (21%) received supplementary injection/s. In the laser treatment phase, median BCVA was 78 letters at baseline (interquartile range 62-80) and decreased by a median of two letters at final visit. In the subset who underwent subsequentinjection treatment, BCVA was 60 letters at first injection, with a median five-letter increase by final visit. Overall outcomes were similar in Indigenous and non-Indigenous Australians. Predictors of reduction in BCVA in the macular laser treatment phase were better baseline BCVA, older age, and PRP treatment (all p < .005). CONCLUSION: Laser treatment for diabetic maculopathy preserved vision in Central Australia, where barriers to follow-up can preclude regular injections. Supplementary injections stabilized vision in the laser-resistant subset.

Long-term survival rates of patients undergoing vitrectomy for diabetic retinopathy in an Australian population: a population-based audit.

IMPORTANCE: Five-year survival rates in patients undergoing vitrectomy for diabetic retinopathy (DR) vary from 68% to 95%. No study has been conducted in an Australian population. BACKGROUND: We aimed to determine the survival rates of patients undergoing diabetic vitrectomy in an Australian population. DESIGN: Retrospective audit, tertiary centre hospitals and private practices. PARTICIPANTS: All individuals in South Australia and the Northern Territory who underwent their first vitrectomy for diabetic complications between January 1, 2007 and December 31, 2011. METHODS: An audit of all eligible participants has been completed previously. Survival status as of July 6, 2018 and cause of death were obtained using SA/NT DataLink. Kaplan-Meier survival curves and multivariate cox-regressions were used to analyse survival rates and identify risk factors for mortality. MAIN OUTCOME MEASURES: Five-, seven- and nine-year survival rates. RESULTS: The 5-, 7- and 9-year survival rates were 84.4%, 77.9% and 74.7%, respectively. The most common cause of death was cardiovascular disease. Associated with increased mortality independent of age were Indigenous ethnicity (HR = 2.04, 95% confidence interval [CI]: 1.17-3.57, P = 0.012), chronic renal failure (HR = 1.76, 95% CI: 1.07-2.89, P = 0.026) and renal failure requiring dialysis (HR = 2.32, 95% CI: 1.25-4.32, P = 0.008). CONCLUSIONS AND RELEVANCE: Long-term survival rates after diabetic vitrectomy in Australia are similar to rates reported in other populations. Indigenous ethnicity and chronic renal failure were the most significant factors associated with long-term mortality. This information can guide allocation of future resources to improve the prognosis of these high risk groups.

Presence of diabetic retinopathy is associated with worse 10-year mortality among Indigenous Australians in Central Australia: The Central Australian ocular health study.

IMPORTANCE: Diabetes mellitus (DM) is highly prevalent among Indigenous Australians and contributes greatly to premature death. The association of diabetic retinopathy (DR) with early mortality, however, has not previously been reported among Indigenous Australians. BACKGROUND: To investigate associations between 10-y mortality and the presence of DR among Indigenous Australians living in Central Australia. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1257 individuals aged 40 y or older, living in one of 30 remote communities within Central Australia were recruited through outreach clinics. METHODS: Fundus examination was performed on all patients at recruitment. The presence of any DR was recorded. MAIN OUTCOME MEASURES: Mortality rate and cause were obtained at 10 y, and their association with any DR was determined. RESULTS: Ten-year all-cause mortality was found to be 29.3%. Of those with DM but no DR, 24.0% died during the 10 y after recruitment, compared with 40.1% for those with any DR (P < 0.0001). Those who had any DR were 75% more likely to die (hazard ratio [HR] 1.75; P < 0.0001) and were more likely to die from renal failure (HR 2.71; P = 0.004) or stroke (HR 5.91; P = 0.026). CONCLUSION AND RELEVANCE: The presence of any DR among those with DM, was associated with a 75% greater 10-y all-cause mortality rate and were more likely to die from renal failure or stroke. We recommend that whenever DR is noted among Indigenous Australians with DM, that they be immediately referred for investigation and management of risk factors, which might predispose to renal failure and stroke.

Association of Visual Impairment and All-Cause 10-Year Mortality Among Indigenous Australian Individuals Within Central Australia: The Central Australian Ocular Health Study.

Importance: It is well established from different population-based studies that visual impairment is associated with increased mortality rate. However, to our knowledge, the association of visual impairment with increased mortality rate has not been reported among indigenous Australian individuals. Objective: To assess the association between visual impairment and 10-year mortality risk among the remote indigenous Australian population. Design, Setting, and Participants: Prospective cohort study recruiting indigenous Australian individuals from 30 remote communities located within the central Australian statistical local area over a 36-month period between July 2005 and June 2008. The data were analyzed in January 2017. Exposures: Visual acuity, slitlamp biomicroscopy, and fundus examination were performed on all patients at recruitment. Visual impairment was defined as a visual acuity of less than 6/12 in the better eye. Main Outcomes and Measures: Mortality rate and mortality cause were obtained at 10 years, and statistical analyses were performed. Hazard ratios for 10-year mortality with 95% confidence intervals are presented. Results: One thousand three hundred forty-seven patients were recruited from a total target population number of 2014. The mean (SD) age was 56 (11) years, and 62% were women. The total all-cause mortality was found to be 29.3% at 10 years. This varied from 21.1% among those without visual impairment to 48.5% among those with visual impairment. After adjustment for age, sex, and the presence of diabetes and hypertension, those with visual impairment were 40% more likely to die (hazard ratio, 1.40; 95% CI, 1.16-1.70; P = .001) during the 10-year follow-up period compared with those with normal vision. Conclusions and Relevance: Bilateral visual impairment among remote indigenous Australian individuals was associated with 40% higher 10-year mortality risk compared with those who were not visually impaired. Resource allocation toward improving visual acuity may therefore aid in closing the gap in mortality outcomes between indigenous and nonindigenous Australian individuals.

Bilateral orbital compartment syndrome in a patient with disseminated intravascular coagulation.

A 39-year-old male developed bilateral periorbital oedema and tense orbits in keeping with orbital compartment syndrome (OCS) shortly after presenting to the emergency department for uncontrollable epistaxis. Bilateral lateral canthotomy and inferior cantholysis was performed within 30 minutes of onset, with the left side further decompressed via superior cantholysis. Computed tomography demonstrated bilateral proptosis and optic nerve stretch, but no intraorbital haemorrhage or haematoma. Laboratory findings were consistent with disseminated intravascular coagulation (DIC) and sepsis of unknown origin. The right visual acuity recovered to 6/6 -2 from counting fingers, but the left eye failed to improve beyond light perception. This unique case of OCS is the first associated with DIC which had no evidence of intraorbital haemorrhage.

Association of disease-specific causes of visual impairment and 10-year mortality amongst Indigenous Australians: the Central Australian Ocular Health Study.

IMPORTANCE: Visual impairment significantly impairs the length and quality of life, but little is known of its impact in Indigenous Australians. BACKGROUND: To investigate the association of disease-specific causes of visual impairment with all-cause mortality. DESIGN: A retrospective cohort analysis. PARTICIPANTS: A total of 1347 Indigenous Australians aged over 40 years. METHODS: Participants visiting remote medical clinics underwent clinical examinations including visual acuity, subjective refraction and slit-lamp examination of the anterior and posterior segments. The major ocular cause of visual impairment was determined. Patients were assessed periodically in these remote clinics for the succeeding 10 years after recruitment. Mortality rates were obtained from relevant departments. MAIN OUTCOME MEASURES: All-cause 10-year mortality and its association with disease-specific causes of visual impairment. RESULTS: The all-cause mortality rate for the entire cohort was 29.3% at the 10-year completion of follow-up. Of those with visual impairment, the overall mortality rate was 44.9%. The mortality rates differed for those with visual impairment due to cataract (59.8%), diabetic retinopathy (48.4%), trachoma (46.6%), 'other' (36.2%) and refractive error (33.4%) (P < 0.0001). Only those with visual impairment from diabetic retinopathy were any more likely to die during the 10 years of follow-up when compared with those without visual impairment (HR 1.70; 95% CI, 1.00-2.87; P = 0.049). CONCLUSIONS AND RELEVANCE: Visual impairment was associated with all-cause mortality in a cohort of Indigenous Australians. However, diabetic retinopathy was the only ocular disease that significantly increased the risk of mortality. Visual impairment secondary to diabetic retinopathy may be an important predictor of mortality.

Visual outcomes following vitrectomy for diabetic retinopathy amongst Indigenous and non-Indigenous Australians in South Australia and the Northern Territory.

IMPORTANCE: Visual outcomes following diabetic vitrectomy have not previously been studied in an Australian population. BACKGROUND: This analysis aimed to determine the rate of, and factors associated with visual success following diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and investigate factors predisposing to early progression to diabetic retinopathy (DR) requiring vitrectomy. DESIGN: Retrospective, population-based audit. PARTICIPANTS: All patients undergoing vitrectomy for the complications of DR in South Australia (SA) and the Northern Territory (NT) between 2007 and 2011. METHODS: Medical records were audited and data collected, including demographics, diabetic history, past treatment for DR, indication for vitrectomy and visual acuity pre and postoperatively. MAIN OUTCOME MEASURES: Visual success (gain of ≥15 ETDRS letters) at 6 and 12 months, postoperatively. RESULTS: A total of 495 diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable or improved vision at 1 year, postoperatively. There was no significant difference between indigenous and non-indigenous eyes achieving visual success (P = 0.929). Timely preoperative laser treatment (P = 0.03) and preoperative visual acuity (P = 0.01) were the predominant factors associated with visual success. CONCLUSIONS AND RELEVANCE: Indigenous patients are just as likely to have improved vision following diabetic vitrectomy as non-Indigenous Australians. However, the small subset of indigenous patients with blind eyes prior to vitrectomy are significantly less likely to improve from surgery. The underlying factors associated with poor outcomes in this group requires further exploration.

FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.

MOTIVATION: Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies. RESULTS: In this study we present an integrative omics approach to group patients based on their altered pathway characteristics and show prognostic differences within breast cancer (p < 9:57E - 10) and glioblastoma multiforme (p < 0:05) patients. We were able validate this approach in secondary RNA-Seq datasets with p < 0:05 and p < 0:01 respectively. We also performed pathway enrichment analysis to further investigate the biological relevance of dysregulated pathways. We compared our approach with network-based classifier algorithms and showed that our unsupervised approach generates more robust and biologically relevant clustering whereas previous approaches failed to report specific functions for similar patient groups or classify patients into prognostic groups. CONCLUSIONS: These results could serve as a means to improve prognosis for future cancer patients, and to provide opportunities for improved treatment options and personalized interventions. The proposed novel graph mining approach is able to integrate PPI networks with gene expression in a biologically sound approach and cluster patients in to clinically distinct groups. We have utilized breast cancer and glioblastoma multiforme datasets from microarray and RNA-Seq platforms and identified disease mechanisms differentiating samples. SUPPLEMENTARY INFORMATION: Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/dysprog.

Ten-year all-cause mortality and its association with vision among Indigenous Australians within Central Australia: the Central Australian Ocular Health Study.

BACKGROUND: No studies to date have explored the association of vision with mortality in Indigenous Australians. We aimed to determine the 10-year all-cause mortality and its associations among Indigenous Australians living in Central Australia. DESIGN: Prospective observational cohort study. PARTICIPANTS: A total of 1257 (93.0%) of 1347 patients from The Central Australian Ocular Health Study, over the age of 40 years, were available for follow-up during a 10-year period. METHODS: All-cause mortality and its associations with visual acuity, age and gender were analysed. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: All-cause mortality was 29.3% at the end of 10 years. Mortality increased as age of recruitment increased: 14.2% (40-49 years), 22.6% (50-59 years), 50.3% (60 years or older) (χ = 59.15; P < 0.00001). Gender was not associated with mortality as an unadjusted variable, but after adjustment with age and visual acuity, women were 17.0% less likely to die (t = 2.09; P = 0.037). Reduced visual acuity was associated with increased mortality rate (5% increased mortality per one line of reduced visual acuity; t = 4.74; P < 0.0001) after adjustment for age, sex, diabetes and hypertension. CONCLUSIONS: The 10-year all-cause mortality rate of Indigenous Australians over the age of 40 years and living in remote communities of Central Australia was 29.3%. This is more than double that of the Australian population as a whole. Mortality was significantly associated with visual acuity at recruitment. Further work designed to better understand this association is warranted and may help to reduce this disparity in the future.

Comparison of trichiasis recurrence after primary bilamellar tarsal rotation or anterior lamellar repositioning surgery performed for trachoma.

BACKGROUND: To compare the trichiasis recurrence rate following bilamellar tarsal rotation or anterior lamellar repositioning, performed as primary surgery for trachomatous trichiasis. DESIGN: Retrospective consecutive case series. PARTICIPANTS: All cases of trachomatous trichiasis undergoing primary surgical correction at Alice Springs Hospital, Alice Springs, Northern Territory, Australia, between 1 June 2001 and 11 June 2011 were included. METHODS: Retrospective chart review. Key baseline, operative and outcome details were collected from the notes. MAIN OUTCOME MEASURE: Recurrent trichiasis was defined as one or more lashes touching the cornea, resulting in recurrent symptoms of trichiasis and warranting further surgery in the opinion of the treating ophthalmologist. RESULTS: Sixty-seven BTR and eighteen ALR procedures were performed, with BTR being performed from 2001 to 2008, and ALR from 2008 to 2011. The mean follow-up times were significantly different for the BTR group (1654 days) and for the ALR group (673 days)(P < 0.001). Kaplan-Meier survival analysis did not reveal any significant differences in recurrence rate between the two procedures overall (P = 0.935). Analysis of the 2008 calendar year (the only year where both procedures were performed and therefore had equal follow-up times) suggested that ALR might have a lower recurrence rate (1/10 ALR recurrences vs. 4/6 BTR recurrences, P = 0.181). CONCLUSIONS: The results do not demonstrate a difference in the recurrence rate between the two techniques. Inconsistent follow times however leave uncertainty in this result, and a larger prospective randomised study is warranted to address this question.

The reliability of single-field fundus photography in screening for diabetic retinopathy: the Central Australian Ocular Health Study.

OBJECTIVE: To assess the accuracy of grading diabetic retinopathy (DR) using single-field digital fundus photography compared with clinical grading from a dilated slit-lamp fundus examination in Indigenous Australians living in Central Australia. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study comparing DR grades in participants with diabetes mellitus presenting for examination at remote community clinics from 1 July 2005 to 30 June 2008. MAIN OUTCOME MEASURES: Sensitivity and specificity of grading using digital photography compared with the clinical gold standard of slit-lamp fundus examination. RESULTS: Of the 1884 participants recruited for the study, 1040 had self-reported diabetes mellitus and, of those, 360 had fundus photographs available (706 eyes) that were able to be graded. On clinical grading, 163 eyes had any DR and 51 eyes had vision-threatening DR (VTDR). The sensitivity and specificity for detecting any DR were 74% (95% CI, 67%-80%) and 92% (95% CI, 90%-94%), respectively. The sensitivity and specificity for detecting VTDR were 86% (95% CI, 77%-96%) and 95% (95% CI, 93%-97%), respectively. CONCLUSION: Single-field digital fundus photography is a valid screening tool for DR in remote communities of central Australia and may be used to provide eye care services to this region with acceptable accuracy.