Applied Epidemiology in Australia

My initial field placement was with the Centre for Disease Control in the Northern Territory where I was employed by the Sexual Health and Blood Borne Virus unit, as the remote sexual health program manager for the Top End from April 2013 to March 2017. I commenced the Master of Philosophy (Applied Epidemiology) program in January 2016, while employed full time in the above position. The Sexual Health and Blood Borne Virus unit are responsible for surveillance, monitoring and management of sexually transmissible infections (STI), HIV and blood borne viruses (BBV) primarily affecting vulnerable Aboriginal populations living in remote communities. A key component of my role was to work with primary health care services in adopting a sexual health quality improvement program to increase STI/BBV testing, identify and treat infections promptly, follow up sexual contacts to minimise transmission and establish systems for improving STI/BBV management. I completed two projects that met core requirement for this degree during this placement. Firstly, I took the lead role on investigating a Salmonella Saintpaul outbreak linked to ready-made meals produced by a restaurant in the Darwin urban area. Secondly, I conducted a data analysis project assessing the epidemiology of hepatitis C in the NT from 1991 to March 2016 which coincided with the introduction of direct-acting antivirals (DAAs) which can cure hepatitis C. From March 2017 to the present, I've been employed by the Sydney local health district at RPA Sexual Health clinic. This thesis includes two projects I've completed that are relevant to this environment. The aim of the first project was to assess chlamydia and gonorrhoea positivity among sexual contacts exposed to these infections that attended publicly funded sexual health services from a variety of urban, inner regional and outer regional and remote areas. The aim of the project was to assess whether the evidence supported adopting a test-and-wait method thereby minimising antibiotic use. The second project was to evaluate the internal HIV surveillance and response system for patients diagnosed with HIV and ongoing care managed by the clinic with a key focus on the information management system used for electronic patient records. All the above projects meet the requirements of this degree

Rehabilitation and return to work after cancer — instruments and practices

The ‘Rehabilitation and return to work after cancer — instruments and practices’ project provides an insight into the issues surrounding rehabilitation and return to work (RTW) after a cancer diagnosis and the problems encountered by workers affected by cancer and their employers. Furthermore, the report presents recommendations for instruments, practices, policies and interventions to successfully support the RTW of workers affected by cancer. Each year, an estimated 3.4 million new cases of cancer are diagnosed in Europe. About half of the people diagnosed with cancer are of working age. Although cancer occurrence differs from one region to another in Europe, the most frequent forms of cancer are breast, colorectal, prostate and lung cancer. These types of cancer were estimated to account for over half of the overall burden of cancer in Europe in 2012. The impact of cancer on a person’s daily life is immediate and striking. The diagnosis usually results in long periods of sickness absence because of medical treatments and functional restrictions. Although, in general, cancer management has improved over the past three decades and the overall number of people who survive cancer is increasing, many cancer survivors still face long-term symptoms and impairments after their treatment ends, such as fatigue. These symptoms and impairments can affect the workability of cancer survivors, making it more difficult to remain in or re-enter the job market. Research shows that most cancer survivors are able to remain in or return to work, but that overall the risk of unemployment among cancer survivors is 1.4 times higher than among people who have never been diagnosed with cancer. Optimising the rehabilitation and RTW of workers affected by cancer is therefore important to both improve the well-being of this vulnerable group and reduce the societal and financial impacts of cancer on European enterprises and society at large. Instruments, practices, policies and interventions aimed at the promotion of rehabilitation and RTW are clearly important. This ‘Rehabilitation and return to work after cancer — instruments and practices’ project reports on the emerging issue of rehabilitation and RTW after cancer and provides national examples of successful instruments, practices, policies and interventions to prevent long-term sickness absences and unemployment. The project is divided into the following main tasks: a literature review on rehabilitation and RTW after a cancer diagnosis; detailed descriptions of instruments, practices, policies and interventions to support rehabilitation and RTW after a cancer diagnosis; company case studies; qualitative research with experts and intermediaries; support for the EU-OSHA stakeholder seminar

ROCK1 and ROCK2 Are Required for Non-Small Cell Lung Cancer Anchorage-Independent Growth and Invasion

Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor anti-tumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases. DLC-1 loss may lead to hyperactivation of RhoA/C and its downstream effectors, the ROCK kinases. We therefore determined whether loss of DLC-1 protein expression identifies non-small cell lung carcinoma (NSCLC) cell lines whose growth and invasion phenotypes are sensitive to ROCK inhibition. We identified and characterized a novel small molecule pharmacologic inhibitor of ROCK and additionally applied genetic approaches to impair ROCK1 and/or ROCK2 activity, and we determined that although NSCLC anchorage-dependent growth was ROCK-independent, both anchorage-independent growth and Matrigel invasion were ROCK-dependent. However, loss of DLC-1 expression did not correlate with ROCK activation or with OXA-06 sensitivity. Unexpectedly, suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their non-overlapping roles in oncogenesis. Mechanistically, the block in anchorage-independent growth was associated with accumulation of cells in the G0/G1 phase of the cell cycle, but not increased anoikis. We conclude that ROCK may be a useful therapeutic target for NSCLC

Strategies to improve control of sexually transmissible infections in remote Australian Aboriginal communities: a stepped-wedge, cluster-randomised trial

BACKGROUND: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. METHODS: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16–34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis . We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12610000358044. FINDINGS: Between April, 2010, and April, 2011, we recruited 68 primary care centres and grouped them into 24 clusters, which were randomly assigned into year 1 clusters (estimated population aged 16–34 years, n=11 286), year 2 clusters (n=10 288), or year 3 clusters (n=13 304). One primary health-care centre withdrew from the study due to restricted capacity to participate. We detected no difference in the relative prevalence of STIs between intervention and control clusters (adjusted relative risk [RR] 0·97, 95% CI 0·84–1·12; p=0·66). However, testing coverage was substantially higher in intervention clusters (22%) than in control clusters (16%; RR 1·38; 95% CI 1·15–1·65; p=0·0006). INTERPRETATION: Our intervention increased STI testing coverage but did not have an effect on prevalence. Additional interventions that will provide increased access to both testing and treatment are required to reduce persistently high prevalences of STIs in remote communities.James Ward, Rebecca J Guy, Alice R Rumbold, Skye McGregor, Handan Wand, Hamish McManus, Amalie Dyda, Linda Garton, Belinda Hengel, Bronwyn J Silver, Debbie Taylor-Thomson, Janet Knox, Basil Donovan, Matthew Law, Lisa Maher, Christopher K Fairley, Steven Skov, Nathan Ryder, Elizabeth Moore, Jacqueline Mein, Carole Reeve, Donna Ah Chee, John Boffa and John M Kaldo

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Распространенность халарового некроза ясеня обыкновенного в Беларуси

Received 30 April 2014, accepted 7 October 2014, published online 27 November 2014Background: Remote Australian Aboriginal communities experience high rates of bacterial sexually transmissible infections (STI). A key strategy to reduce STIs is to increase testing in primary health care centres. The current study aimed to explore barriers to offering and conducting STI testing in this setting. Methods: A qualitative study was undertaken as part of the STI in Remote communities, Improved and Enhanced Primary Health Care (STRIVE) project; a large cluster randomised controlled trial of a sexual health quality improvement program. We conducted 36 in-depth interviews in 22 participating health centres across four regions in northern and central Australia. Results: Participants identified barriers including Aboriginal cultural norms that require the separation of genders and traditional kinship systems that prevent some staff and patients from interacting, both of which were exacerbated by a lack of male staff. Other common barriers were concerns about client confidentiality (lack of private consulting space and living in small communities), staff capacity to offer testing impacted by the competing demands for staff time, and high staff turnover resulting in poor understanding of clinic systems. Many participants also expressed concerns about managing positive test results. To address some of these barriers, participants revealed informal strategies, such as team work, testing outside the clinic and using adult health checks. Conclusions: Results identify cultural, structural and health system issues as barriers to offering STI testing in remote communities, some of which were overcome through the creativity and enthusiasm of individuals rather than formal systems. Many of these barriers can be readily addressed through strengthening existing systems of cultural and clinical orientation and educating staff to view STI in a population health framework. However others, particularly issues in relation to culture, kinship ties and living in small communities, may require testing modalities that do not rely on direct contact with health staff or the clinic environment.Belinda Hengel, Rebecca Guy, Linda Garton, James Ward, Alice Rumbold, Debbie Taylor-Thomson, Bronwyn Silver, Skye McGregor, Amalie Dyda, Janet Knox, John Kaldor, Lisa Maher and on behalf of the STRIVE Investigator

Coinfection with Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis: a crosssectional analysis of positivity and risk factors in remote Australian Aboriginal communities

Objectives To determine the co-occurrence and epidemiological relationships of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) in a high-prevalence setting in Australia.Methods In the context of a cluster randomised trial in 68 remote Aboriginal communities, we obtained laboratory reports on simultaneous testing for CT, NG and TV by nucleic acid amplification tests in individuals aged ≥16 years and examined relationships between age and sex and the coinfection positivity. ORs were used to determine which infections were more likely to co-occur by demographic category.Results Of 13 480 patients (median age: 30 years; men: 37%) tested for all three infections during the study period, 33.3% of women and 21.3% of men had at least one of them, highest in patients aged 16–19 years (48.9% in women, 33.4% in men). The most frequent combination was CT/NG (2.0% of women, 4.1% of men), and 1.8% of women and 0.5% of men had all three. In all co-combinations, coinfection positivity was highest in patients aged 16–19 years. CT and NG were highly predictive of each other\u27s presence, and TV was associated with each of the other two infections, but much more so with NG than CT, and its associations were much stronger in women than in men.Conclusions In this remote high-prevalence area, nearly half the patients aged 16–19 years had one or more sexually transmitted infections. CT and NG were more common dual infections. TV was more strongly associated with NG coinfections than with CT. These findings confirm the need for increased simultaneous screening for CT, NG and TV, and enhanced control strategies

Incidence of curable sexually transmissible infections among adolescents and young adults in remote Australian Aboriginal communities: analysis of longitudinal clinical service data

Objectives To undertake the first comprehensive analysis of the incidence of three curable sexually transmissible infections (STIs) within remote Australian Aboriginal populations and provide a basis for developing new control initiatives.Methods We obtained all results for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) testing conducted during 2009–2011 in individuals aged ≥16 years attending 65 primary health services across central and northern Australia. Baseline prevalence and incidence of all three infections was calculated by sex and age group.Results A total of 17 849 individuals were tested over 35 months. Baseline prevalence was 11.1%, 9.5% and 17.6% for CT, NG and TV, respectively. During the study period, 7171, 7439 and 4946 initially negative individuals had a repeat test for CT, NG and TV, respectively; these were followed for 6852, 6981 and 6621 person-years and 651 CT, 609 NG and 486 TV incident cases were detected. Incidence of all three STIs was highest in 16-year-olds to 19-year-olds compared with 35+ year olds (incident rate ratio: CT 10.9; NG 11.9; TV 2.5). In the youngest age group there were 23.4 new CT infections per 100 person-years for men and 29.2 for women; and 26.1 and 23.4 new NG infections per 100 person-years in men and women, respectively. TV incidence in this age group for women was also high, at 19.8 per 100 person-years but was much lower in men at 3.6 per 100 person-years.Conclusions This study, the largest ever reported on the age and sex specific incidence of any one of these three curable infections, has identified extremely high rates of new infection in young people. Sexual health is a priority for remote communities, but will clearly need new approaches, at least intensification of existing approaches, if a reduction in rates is to be achieved