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Objectives: The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. Methods: A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982–1995, 1996–1999, 2000–2004, 2005–2008 and 2009–2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. Results: For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend < 0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend < 0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. Conclusions: Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

In recent years, prevalence of Human Immunodeficiency Virus (HIV) has increased sub-stantially in Bali, Indonesia, in men who have sex with men (MSM) and transgender women, known locally as ‘waria’. There are limited behavioural data in this population. We conducted a behavioural survey of MSM/waria in Bali in March–April 2018. Respondents were primarily recruited by HIV outreach workers. Respondents reported details about anal intercourse events with their last male/waria romantic partner and/or last male/waria casual partner (respondents could report on both if relevant). Statistical significance was tested with generalised estimating equations. Among 709 participants, median age was 27 (interquartile range = 24–31), and 92.1% were male and 7.9% were waria. One-third were born in Bali. Overall, 85.9% had ever had an HIV test; 55.1% reported being HIV-negative, 15.0% HIV-positive, and 30.0% had unknown serostatus. Most (86.5%) reported sex with men, 9.5% with waria, and 20.0% with women in the previous 6 months. Respondents described 703 anal intercourse events (397/306 with romantic/casual partners, re-spectively; 191 reported on both). Over half (56.5%) of the events were protected by condoms and 7.3% by biomedical prevention (2.6% by PrEP in either partner, 4.7% by HIV treatments in either partner). Thus, 36.3% of events involved unprotected condomless anal intercourse (40.8%/30.4% in romantic/casual partners, respectively). In multivariate analysis, unprotected condomless anal intercourse events were associated with romantic partners (p < 0.001), being born in Bali (p = 0.002), lower education (p = 0.013), believing that withdrawal before ejaculation is effective (p < 0.001), liking to use withdrawal (p = 0.021), and not liking condoms (p < 0.001). One-quarter of events had potentially reduced HIV transmission risk through non-condom-based risk reduction strategies, while 11.1% had no potential risk reduction. Events presenting the highest potential risk of HIV

Background A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. Methods Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). Findings Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. Interpretation In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. Funding This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

Correct catheter position is crucial to ensuring appropriate function of the catheter and avoid complications. This paper describes a dataset consisting of 50,612 image level and 17,999 manually labelled annotations from 30,083 chest radiographs from the publicly available NIH ChestXRay14 dataset with manually annotated and segmented endotracheal tubes (ETT), nasoenteric tubes (NET) and central venous catheters (CVCs).Copyright © 2021. Crown.

Learning Objectives: 1. To describe the common data elements for structured reporting of Cervical spine trauma per the AO classification 2. Identify the minimum data set required to develop a deep learning model for AO classification of C-spine trauma Background: Cervical spine traumatic injuries have historically had limited consensus around management, partly from the lack of any universally accepted classification. Recent literature supports the use of the AOSpine Trauma classification to improve communication between clinicians.1,5,6,7 While the AOSpine classification can be cumbersome to report, the use of synoptic reporting can assist, using standardised nomenclature, universally required findings and a consistent report structure for the purpose of developing robust deep learning models.4,8 Imaging Findings: C-spine trauma is classified into upper C-spine consisting of C0-C3 and lower C-spine (or subaxial spine) which consists of C3-7. 3 items are included to explain the injury severity and prognosis-1. Injury morphology (type A-C bony injuries; additionally, type F and BL for subaxial) 2. Neurological status (N0-4) 3. Clinical modifiers (M1-4) Imaging is used to classify injury morphology-with fractures classified as type A, B or C. In the Upper C-Spine, the first step is to identify the fractured bone and joint (C0-C2), followed by the type. Type A injuries include isolated bony injuries only (usually stable injuries); type B include ligamentous injuries (potentially unstable injuries); type C include any displacement, translation or instability-suggesting unstable injuries.1,2 Subaxial injuries are classified as type A for compression bony injuries, type B for tension band injuries, type C consist of any displacement or translation. Additionally, the subaxial classification incorporates type F for facet injuries; while type BL is used for 'Bilateral injuries'.1,3 If multiple injuries are present, the most severe injury's grading is given. The neurological

Background: Persons living with human immunodeficiency virus (HIV) are at elevated risk of developing the malignant diseases that require allogeneic stem cell transplantation (ASCT). Recent data suggest that these individuals are also at an elevated risk of certain complications post-ASCT. This risk may result from preexisting HIV-related factors affecting dynamics of immune reconstitution post-ASCT. However, to date, there has been little work describing the dynamics of immune reconstitution post-ASCT in persons with HIV and none comparing these data to controls without HIV. Methods: We assessed T-cell reconstitution in 6 ASCT with HIV recipients (HIV+ASCT) compared to a control population of 21 ASCT without HIV recipients. In a subset of HIV+ASCT recipients we performed additional flow cytometry profiling of CD8+ T-cell subsets and antigen specificity of reconstituting CD4+ and CD8+ T cells. Results: We observe no difference in post-ASCT CD4+ T cells between HIV+ASCT and HIV-negative ASCT recipients, despite much lower pre-ASCT CD4+ T-cell counts in the HIV+ASCT group. In contrast, we observed significantly higher CD8+ T-cell numbers in the HIV+ASCT group post-ASCT. The reconstituting CD8+ T-cells were predominantly CD45RO+, whereas homing markers and antigen specificity of these cells varied between participants. Conclusion: This study represents the most extensive characterization of immune-reconstitution post-ASCT in persons with HIV, and the first to our knowledge to compare these data to ASCT controls without HIV. The results indicate that immune reconstitution in this group can be affected by preexisting HIV infection and post-ASCT antigen exposure.

Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. Objectives: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. Methods: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case–control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. Results: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. Conclusions: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

BACKGROUND: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. METHODS: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). FINDINGS: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. INTERPRETATION: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. FUNDING: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

A history of concussion has been linked to long-term cognitive deficits; however, the neural underpinnings of these abnormalities are poorly understood. This study recruited 26 asymptomatic male Australian footballers with a remote history of concussion (i.e. at least six months since last concussion), and 23 non-collision sport athlete controls with no history of concussion. Participants completed three ocular motor tasks (prosaccade, antisaccade and a cognitively complex switch task) to assess processing speed, inhibitory control and cognitive flexibility, respectively. Diffusion tensor imaging data were acquired using a 3 T MRI scanner, and analysed using tract-based spatial statistics, to investigate white matter abnormalities and how they relate to ocular motor performance. Australian footballers had significantly slower adjusted antisaccade latencies compared to controls (P = 0.035). A significant switch cost (i.e. switch trial error > repeat trial error) was also found on the switch task, with Australian footballers performing increased magnitude of errors on prosaccade switch trials relative to prosaccade repeat trials (P = 0.023). Diffusion tensor imaging analysis found decreased fractional anisotropy, a marker of white matter damage, in major white matter tracts (i.e. corpus callosum, corticospinal tract) in Australian footballers relative to controls. Notably, a larger prosaccade switch cost was significantly related to reduced fractional anisotropy in anterior white matter regions found to connect to the prefrontal cortex (i.e. a key cortical ocular motor centre involved in executive functioning and task switching). Taken together, Australian footballers with a history of concussion have ocular motor deficits indicative of poorer cognitive processing speed and cognitive flexibility, which are related to reduce white matter integrity in regions projecting to important cognitive ocular motor structures. These findings provide novel insights into the neural

INTRODUCTION: Neoadjuvant radiotherapy (NART) as part of a multi-modality approach for locally advanced breast cancer (LABC) requires further investigation. Importantly, this approach may allow for a single-staged surgical procedure, with mastectomy and immediate autologous reconstruction. Multiple other potential benefits of NART include improved pathological downstaging of breast disease, reduced overall treatment time, elimination of time period with breast tissue deficit and improved patient satisfaction. METHODS: This is a retrospective multi-institutional review of patients with LABC and high-risk breast disease undergoing NART. Eligible patients sequentially underwent neoadjuvant chemotherapy (NACT) with or without HER2-targeted therapy, NART, followed by mastectomy with immediate autologous breast reconstruction (BR) 4- to 6 weeks post-completion of radiotherapy. Patient and tumour characteristics were analysed using descriptive statistics. Surgical complications were assessed using the Clavien-Dindo Classification (Ann Surg 2004; 240: 205). RESULTS: From 3/2013 to 9/2019, 153 patients were treated with NART. The median age was 47 years (IQR 42-52), with median body mass index of 27. Eighteen patients experienced Grade 3 acute surgical complications. This included 13 Grade 3B breast-site events and 9 Grade 3B donor-site events, where further surgical intervention was required for management of wound infection, wound dehiscence, flap or mastectomy skin necrosis, haematoma and internal mammary venous anastomotic thrombosis. No autologous flap loss was observed. CONCLUSION: Neoadjuvant radiotherapy facilitates a single-stage surgical procedure with mastectomy and immediate autologous BR, eliminating the delay to reconstructive surgery and thus shortening a woman's breast cancer journey. The findings of this review support the use of NART, with comparable rates of surgical complications to standard sequencing.

INTRODUCTION: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder for which there are currently no disease-modifying therapies. The neuropathology of PSP is associated with the accumulation of hyperphosphorylated tau in the brain. We have previously shown that protein phosphatase 2 activity in the brain is upregulated by sodium selenate, which enhances dephosphorylation. Therefore, the objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying therapy for PSP. METHODS AND ANALYSIS: This will be a multi-site, phase 2b, double-blind, placebo-controlled trial of sodium selenate. 70 patients will be recruited at six Australian academic hospitals and research institutes. Following the confirmation of eligibility at screening, participants will be randomised (1:1) to receive 52 weeks of active treatment (sodium selenate; 15 mg three times a day) or matching placebo. Regular safety and efficacy visits will be completed throughout the study period. The primary study outcome is change in an MRI volume composite (frontal lobe+midbrain-3rd ventricle) over the treatment period. Analysis will be with a general linear model (GLM) with the MRI composite at 52 weeks as the dependent variable, treatment group as an independent variable and baseline MRI composite as a covariate. Secondary outcomes are change in PSP rating scale, clinical global impression of change (clinician) and change in midbrain mean diffusivity. These outcomes will also be analysed with a GLM as above, with the corresponding baseline measure entered as a covariate. Secondary safety and tolerability outcomes are frequency of serious adverse events, frequency of down-titration occurrences and frequency of study discontinuation. Additional, as yet unplanned, exploratory outcomes will include analyses of other imaging, cognitive and biospecimen measures. ETHICS AND DISSEMINATION: The study was approved by the Alfred Health Ethics Committee (594/20). Each