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Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

BACKGROUND: The development of high-throughput drug screening (HTS) using primary cultures provides a promising, clinically translatable approach to tailoring treatment strategies for patients with cancer. However, this has been challenging for solid tumors because of often limited amounts of tissue available. In most cases, in vitro expansion is required before HTS, which may lead to overgrowth and contamination by non-neoplastic cells. METHODS: In this study, hematoxylin and eosin staining and immunohistochemical staining were performed on 129 cytopathology cases from 95 patients. These cytopathology cases comprised cell block preparations derived from primary tumor specimens or patient-derived xenografts as part of a pediatric precision oncology trial. Cytopathology cases were compared with the morphology and immunohistochemical staining profile of the original tumor. Cases were reported as tumor cells present, equivocal, or tumor cells absent. The HTS results from cytopathologically validated cultures were incorporated into a multidisciplinary tumor board report issued to the treating clinician to guide clinical decision making. RESULTS: On cytopathologic examination, tumor cells were present in 77 of 129 cases (60%) and were absent in 38 of 129 cases (29%), whereas 14 of 129 cases (11%) were equivocal. Cultures that contained tumor cells resembled the tumors from which they were derived. CONCLUSIONS: Cytopathologic examination of tumor cell block preparations is feasible and provides detailed morphologic characterization. Cytopathologic examination is essential for ensuring that samples submitted for HTS contain representative tumor cells and that in vitro drug sensitivity data are clinically translatable.

OBJECTIVE: To assess the sensitivity and specificity of clinical breast examination for detecting breast cancer in asymptomatic women with predisposing germline mutations enrolled in a cancer risk management program that includes radiologic screening. DESIGN, SETTING: Retrospective, longitudinal cohort study of women with BRCA1/2 mutations who attended the Breast and Ovarian Cancer Risk Management Clinic at the Peter MacCallum Cancer Centre, a tertiary referral centre in Melbourne, during 1 September 2001 - 31 December 2019. PARTICIPANTS: Consecutive women with BRCA1/2 mutations who did not have personal histories of cancer and had not undergone bilateral risk-reducing mastectomy, and who had visited the clinic at least twice during the study period. Participants had generally undergone breast examination at 6- or 12-month intervals, and annual breast imaging (mammography; and magnetic resonance imaging [MRI] for women aged 50 years or younger). MAIN OUTCOME MEASURES: Sensitivity (proportion of all biopsy-confirmed breast cancers detected by breast examination alone) and specificity of breast examination for detecting breast cancer. RESULTS: Of 414 eligible women (mean age, 35.5 years; SD, 11.2 years), 35 were diagnosed with breast cancer during 1761 woman-years of follow-up. Only two were diagnosed based on breast examination alone (ie, without radiologic evidence), neither of whom was undergoing MRI screening. The sensitivity of breast examination was 6% (95% CI, 1-19%), the specificity 97% (95% CI, 95-98%); the positive predictive value was 14% (95% CI, 2-43%), the negative predictive value 92% (95% CI, 89-94%). CONCLUSION: Clinical breast examination did not increase the number of breast cancers detected in MRI-screened women with BRCA1/2 mutations. Removing breast examination from surveillance programs that include MRI may be reasonable for these women.

Photo‐mediation offers unparalleled spatiotemporal control over controlled radical polymerizations (CRP). Photo‐induced electron/energy transfer reversible addition–fragmentation chain transfer (PET‐RAFT) polymerization is particularly versatile owing to its oxygen tolerance and wide range of compatible photocatalysts. In recent years, broadband‐ and near‐infrared (NIR)‐mediated polymerizations have been of particular interest owing to their potential for solar‐driven chemistry and biomedical applications. In this work, we present the first example of a novel photocatalyst for both full broadband‐ and NIR‐mediated CRP in aqueous conditions. Well‐defined polymers were synthesized in water under blue, green, red, and NIR light irradiation. Exploiting the oxygen tolerant and aqueous nature of our system, we also report PET‐RAFT polymerization at the microliter scale in a mammalian cell culture medium.

IMPORTANCE: National data on eye health-care service utilization will inform Australia's eye health policy. BACKGROUND: To investigate the utilization of eye health-care services by Australians. DESIGN: Cross-sectional survey. PARTICIPANTS: Indigenous Australians aged 40 years and older and non-Indigenous Australians aged 50 years and older. METHODS: One thousand seven hundred thirty-eight Indigenous Australians and 3098 non-Indigenous Australians were recruited from 30 randomly selected sites, stratified by remoteness. Sociodemographic, ocular history and eye health-care service utilization data were collected, and an eye examination was conducted. MAIN OUTCOME MEASURES: Recentness of eye examinations, types of providers used and associated risk factors. RESULTS: Approximately 67.0% of Indigenous Australians and 82.5% of non-Indigenous Australians underwent an eye examination within the previous 2 years. Indigenous status (P < 0.001), male gender (P < 0.001), Outer Regional (P < 0.001) and Very Remote (P < 0.001) residence were associated with less recent examinations. Participants with >self-reported eye disease or diabetes were most likely to have been examined within the past year (P < 0.001). For Indigenous Australians, older age was associated with recent eye testing (P = 0.001). Those with retinal disease and cataract were more likely to see an ophthalmologist (P < 0.001), and those with refractive error were more likely to see an optometrist (P < 0.001). In Regional Australia, non-Indigenouspeople were more likely to see optometrists (P < 0.001), and Indigenous Australians were more likely to utilize other, non-specialistservices (P < 0.001). CONCLUSIONS AND RELEVANCE: Eye examination frequency has improved in Indigenous and non-Indigenous Australians compared with previous population-based research. Further improvements are required in risk groups including Indigenous Australians and those living in Regional and Remote areas.

IMPORTANCE: In Australia, knowledge of the epidemiology of retinal vein occlusion remains scarce because of a paucity of recent population-based data. The National Eye Health Survey (2015-2016) provides an up-to-date estimate of the prevalence of retinal vein occlusion in non-Indigenous and Indigenous Australian adults. BACKGROUND: To determine the prevalence and associations of retinal vein occlusion in a national sample of Indigenous and non-Indigenous Australian adults. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 3098 non-Indigenous Australians (aged 50-98 years) and 1738 Indigenous Australians (aged 40-92 years) living in 30 randomly selected sites, stratified by remoteness. METHODS: Retinal vein occlusions were graded from retinal photographs using standardized protocols and recorded as central retinal vein occlusion or branch retinal vein occlusion. MAIN OUTCOME MEASURE: Prevalence of retinal vein occlusion. RESULTS: In the non-Indigenous population, the sampling weight adjusted prevalence of any retinal vein occlusion was 0.96% (95% confidence interval: 0.59, 1.6), with branch retinal vein occlusion observed in 0.72% (95% confidence interval: 0.41, 1.2) and central retinal vein occlusion in 0.24% (95% confidence interval: 0.13, 0.47). Any retinal vein occlusion was found in 0.91% (95% confidence interval: 0.47, 1.7) of Indigenous Australians aged 40 years and over, with branch retinal vein occlusion observed in 0.83% (95% confidence interval: 0.40, 1.7) and central retinal vein occlusion in 0.07% (95% confidence interval: 0.02, 0.32). Older age (odds ratio = 1.64 per 10 years, P = 0.006) and the presence of self-reported diabetes (odds ratio = 3.24, P = 0.006) were associated with any retinal vein occlusion after multivariable adjustments. Retinal vein occlusion was attributed as the cause of monocular vision loss (<6/12) in seven (0.25%) non-Indigenous and six (0.36%) Indigenous participants. CONCLUSIONS AND RELEVANCE: These data

BACKGROUND: To describe the clinical characteristics of non-English speaking patients from the Diabetes Management Project (NEDMP), and compare their diabetes management and severity of diabetic retinopathy (DR) with the English-speaking DMP sample (EDMP). DESIGN: A prospective study was conducted on non-English speaking adults with diabetes who attended the Royal Victorian Eye and Ear Hospital. PARTICIPANTS: 136 (90.1%) non-English speaking adults were assessed, with a mean age of 72.2 years (range: 50-88 years); 74 (54.4%) were male. METHODS: Participants completed interviewer-administered questionnaires and underwent visual acuity, fundus photography, optical coherence tomography, biochemistry and anthropometric measurements. The EDMP assessed 609 patients in 2009 using a similar protocol. MAIN OUTCOME MEASURES: Type and duration of diabetes, diabetes control and diabetic retinopathy. RESULTS: A total of 127 (93.4%) and 8 (5.9%) participants reported having type 2 and type 1 diabetes, respectively, with a median (IQR) duration of 17 (14) years. The proportion of patients with poor diabetes control (HbA1c ≥ 7%) in the NEDMP was similar to the EDMP (64.0% and 68.2%, respectively; P = 0.411). A significantly higher proportion of patients with DR in the NEDMP were found to have poor diabetes control (HbA1c ≥ 7%) compared to those without DR (80.9% vs. 50.0%, P = 0.003). Almost two-thirds of NEDMP patients (74/118) had DR and 23% (27/115) had diabetic macular edema. The prevalence of DR was similar between the NEDMP and EDMP studies, ranging from 25-30% and 28-29%. CONCLUSIONS: The clinical characteristics, diabetes control, and DR severity of English and non-English-speaking patients were similar. The high proportion of poor diabetes management in non-English speaking patients with DR suggests educational and behavioural interventions to improve glycaemic control are warranted.

OBJECTIVE: To determine adherence to NHMRC eye examination guidelines for Indigenous and non-Indigenous Australian people with diabetes. DESIGN: Cross-sectional survey using multistage, random cluster sampling. SETTING: Thirty randomly selected geographic sites in the five mainland Australian states and the Northern Territory, stratified by remoteness. PARTICIPANTS: 1738 Indigenous Australians aged 40-92 years and 3098 non-Indigenous Australians aged 50-98 years were recruited and examined between March 2015 and April 2016 according to a standardised protocol that included a questionnaire (administered by an interviewer) and a series of standard eye tests. MAIN OUTCOME MEASURES: Adherence rates to NHMRC eye examination guidelines; factors influencing adherence. RESULTS: Adherence to screening recommendations was significantly greater among non-Indigenous Australians (biennial screening; 77.5%) than Indigenous Australians (annual screening; 52.7%; P < 0.001). Greater adherence by non-Indigenous Australians was associated with longer duration of diabetes (adjusted odds ratio [aOR], 1.19 per 5 years; P = 0.018), while increasing age was associated with poorer adherence in non-Indigenous Australians (aOR, 0.70 per decade; P = 0.011). For Indigenous Australians, residing in inner regional areas (aOR, 1.66; P = 0.007) and being male (aOR, 1.46; P = 0.018) were significant factors positively associated with adherence. CONCLUSIONS: More than three-quarters of non-Indigenous Australians with diabetes and more than half of Indigenous Australians with diabetes adhere to the NHMRC eye examination guidelines. The discrepancy between the adherence rates may point to gaps in the provision or uptake of screening services in Indigenous communities, or a lack of awareness of the guidelines. A carefully integrated diabetic retinopathy screening service is needed, particularly in remote areas, to improve adherence rates.