Factors impacting resident outcomes from COVID-19 outbreaks in Residential Aged Care Facilities in Sydney Local Health District: testing an infection prevention and control scoring system.

BACKGROUND: COVID-19 outbreaks have disproportionately affected Residential Aged Care Facilities (RACFs) around the world, with devastating impacts for residents and their families. Many factors such as community prevalence, facility layout, and infection control practices have been linked to resident outcomes. At present, there are no scoring systems designed to quantify these factors and assess their level of association with resident attack rates and mortality rates. METHODS: We constructed a novel Infection Prevention and Control (IPC) scoring system to quantify facility layout, ability to cohort residents, and IPC practices in RACFs. We conducted a retrospective observational cohort study of COVID-19 outbreaks, applying our IPC scoring system to all COVID-19 outbreaks occurring in RACFs in Sydney Local Health District during the Delta and Omicron waves of the COVID-19 pandemic in New South Wales, Australia. RESULTS: Twenty-six COVID-19 outbreaks in 23 facilities in the Delta wave, and 84 outbreaks in 53 facilities in the Omicron wave were included in the study. A linear Generalised Estimating Equation model was fitted to the Omicron data. Higher IPC scores were associated with higher attack rates and mortality rates. Facilities with IPC scores greater than 75.0% had attack rates 19.6% higher [95% CI: 6.4%-32.8%] and mortality rates 1.7% higher [95% CI: 0.6%-2.7%] than facilities with an IPC score of less than 60.0%. CONCLUSIONS: The results of this study suggest the utility of the IPC scoring system for identifying facilities at greater risk of adverse outcomes from COVID-19 outbreaks. While further validation and replication of accuracy is required, the IPC scoring system could be used and adapted to improve planning, policy, and resource allocation for future outbreaks.

Direct Measurement of a Biomarker's Native Optimal Frequency with Physical Adsorption Based Immobilization.

The optimal frequency (OF) of a biomarker in electrochemical impedance spectroscopy (EIS) is the frequency at which the EIS response best reflects the binding of the biomarker to its molecular recognition element. Commonly, biosensors rely on complicated immobilization chemistry to attach biological molecules to the sensor surface, making the direct study of a biomarker's native OF a challenge. Physical adsorption presents a simple immobilization strategy to study the native biomarker's OF, but its utility is often discouraged due to a loss in biological activity. To directly study a biomarker's native OF and investigate the potential of OF to overcome the limitations of physical adsorption, a combination of EIS and glutaraldehyde-mediated physical adsorption was explored. The experimental sensing platform was prepared by immobilizing either anti-lactoferrin (Lfn) IgG or anti-immunoglobulin E (IgE) onto screen printed carbon electrodes. After characterizing the native OFs of both biomarkers, investigation of the platform's specificity, stability, and performance in complex medium was found to be sufficient. Finally, a paper-based tear sampling component was integrated to transform the testing platform into a prototypical point-of-care dry eye diagnostic. The investigation of native OFs revealed a correlation between the native OFs (57.44 and 371.1 Hz for Lfn and IgE, respectively) and the molecular weight of the antibody-antigen complex. Impedance responses at the native OFs have enabled detection limits of 0.05 mg/mL and 40 ng/mL for Lfn and IgE, respectively, covering the clinically relevant ranges. The native OFs were found to be robust across various testing mediums and conditions.

Flow-perfusion bioreactor system for engineered breast cancer surrogates to be used in preclinical testing.

There is a need for preclinical testing systems that predict the efficacy, safety and pharmacokinetics of cancer therapies better than existing in vitro and in vivo animal models. An approach to the development of predictive in vitro systems is to more closely recapitulate the cellular and spatial complexity of human cancers. One limitation of using current in vitro systems to model cancers is the lack of an appropriately large volume to accommodate the development of this complexity over time. To address this limitation, we have designed and constructed a novel flow-perfusion bioreactor system that can support large-volume, engineered tissue comprised of multicellular cancer surrogates by modifying current microfluidic devices. Key features of this technology are a three-dimensional (3D) volume (1.2 cm3 ) that has greater tissue thickness than is utilized in existing microfluidic systems and the ability to perfuse the volume, enabling the development of realistic tumour geometry. The constructs were fabricated by infiltrating porous carbon foams with an extracellular matrix (ECM) hydrogel and engineering through-microchannels. The carbon foam structurally supported the hydrogel and microchannel patency for up to 161 h. The ECM hydrogel was shown to adhere to the carbon foam and polydimethylsiloxane flow chamber, which housed the hydrogel-foam construct, when surfaces were coated with glutaraldehyde (carbon foam) and nitric acid (polydimethylsiloxane). Additionally, the viability of breast cancer cells and fibroblasts was higher in the presence of perfused microchannels in comparison to similar preparations without microchannels or perfusion. Therefore, the flow-perfusion bioreactor system supports cell viability in volume and stromal contexts that are physiologically-relevant. Copyright © 2015 John Wiley & Sons, Ltd.

Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11µg/cm(2)h and 108±7µg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4µg/cm(2)h, p<0.05) or solution formulation (44±6µg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics.

Community-based prevention of hepatitis-B-related liver cancer: Australian insights.

PROBLEM: Although most primary hepatocellular cancers (HCCs) are attributable to chronic viral hepatitis and largely preventable, such cancers remain a leading cause of cancer-related mortality wherever chronic hepatitis B is endemic. APPROACH: Many HCCs could be prevented by increasing awareness and knowledge of hepatitis B, optimizing the monitoring of chronic hepatitis B and using antiviral treatments - but there are gaps in the implementation of such strategies. LOCAL SETTING: The "B Positive" programme, based in Sydney, Australia, is designed to improve hepatitis-B-related health outcomes among immigrants from countries with endemic hepatitis B. The programme offers information about disease screening, vaccination and treatment options, as well as optimized access to care. RELEVANT CHANGES: The B Positive programme has been informed by economic modelling. The programme offers culturally tailored education on chronic hepatitis B to target communities and their health practitioners and regular follow-up through a population-based registry of cases. LESSONS LEARNT: As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, optimizing access to treatment seems an appropriate and cost-effective management option. The identification and accurate staging of cases and the judicious use of antiviral medications are predicated upon an informed and educated health workforce. As establishing community trust is a lengthy process, delaying the implementation of programmes against chronic hepatitis B until antiviral drugs become cheaper is unwarranted.

Cancer incidence and mortality in people aged less than 75 years: changes in Australia over the period 1987-2007.

BACKGROUND: Australia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified. METHODS: We used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age-sex specific rates (average of 1986-1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006-2008). We limited the analyses to people aged less than 75 years. RESULTS: There was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (-2259), bowel (-1797), breast (-773) and stomach (-577). Other notable falls were for cancers of the prostate (-295), cervix (-242) and non-Hodgkin lymphoma (-240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (-1705), bladder (-1110) and unknown primary (-904). CONCLUSIONS: The reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.

Cost of treating chronic hepatitis B: comparison of current treatment guidelines.

AIM: To compare program costs of chronic hepatitis B (CHB) screening and treatment using Australian and other published CHB treatment guidelines. METHODS: Economic modeling demonstrated that in Australia a strategy of hepatocellular cancer (HCC) prevention in patients with CHB is more cost-effective than current standard care, or HCC screening. Based upon this model, we developed the B positive program to optimize CHB management of Australians born in countries of high CHB prevalence. We estimated CHB program costs using the B positive program algorithm and compared them to estimated costs of using the CHB treatment guidelines published by the Asian-Pacific, American and European Associations for the Study of Liver Disease (APASL, AASLD, EASL) and those suggested by an independent United States hepatology panel. We used a Markov model that factored in the costs of CHB screening and treatment, individualized by viral load and alanine aminotransferase levels, and calculated the relative costs of program components. Costs were discounted by 5% and calculated in Australian dollars (AUD). RESULTS: Using the B positive algorithm, total program costs amount to 13,979,224 AUD, or 9634 AUD per patient. The least costly strategy is based upon using the AASLD guidelines, which would cost 34% less than our B positive algorithm. Using the EASL and the United States Expert Group guidelines would increase program costs by 46%. The largest expenditure relates to the cost of drug treatment (66.9% of total program costs). The contribution of CHB surveillance (20.2%) and HCC screening and surveillance (6.6%) is small--and together they represent only approximately a quarter of the total program costs. CONCLUSION: The significant cost variations in CHB screening and treatment using different guidelines are relevant for clinicians and policy makers involved in designing population-based disease control programs.

PET imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133).

Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand (18)F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of (18)F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that (18)F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.

What has fairness got to do with it? Tackling tobacco among Australia's disadvantaged.

ISSUE: While population wide smoking rates are falling steadily the rates remain high among the disadvantaged. The future we face is one where the differentials in smoking rates will continue to widen and will flow through to increased health inequalities. APPROACH: How best to reduce smoking rates among the disadvantaged? Alongside existing population level initiatives and social policy initiatives is an urgent need for a targeted, comprehensive approach that acknowledges the serious impact of smoking on the disadvantaged. In 2006 Cancer Council NSW embarked on a statewide, multi-component Tackling Tobacco Program to encourage and support non-government social and community services to address smoking among their clients. KEY FINDINGS: Tackling Tobacco Program results have shown that the 1600 staff from 400 organisations trained to provide smoking care can attain the knowledge and confidence to address tobacco and that clients are very receptive to receiving quit support from them. Improvements in quality of life for clients who do quit have been encouraging and the Tackling Tobacco Program has challenged assumptions and attitudes that disadvantaged people are uninterested and unable to quit. IMPLICATIONS: Alongside population and social policy approaches must be a serious investment in tackling smoking among the disadvantaged. CONCLUSIONS: Tackling Tobacco Program is an innovative example of how to engage disadvantaged smokers, de-normalise smoking and encourage and support quitting using familiar settings. Engaging Australia's large network of social and community services as allies in this work should be vigorously pursued.

Using a population-based approach to prevent hepatocellular cancer in New South Wales, Australia: effects on health services utilisation.

BACKGROUND: Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the B Positive pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area. METHODS: Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program. RESULTS: Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations. CONCLUSIONS: While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence.

Anywhere, anytime: retail access to tobacco in New South Wales and its potential impact on consumption and quitting.

Relatively little attention has been given to the retail availability of tobacco products despite the likelihood that ubiquitous supply may represent a primary form of tobacco promotion in Australia. This study aimed to explore the number and distribution of tobacco outlets, smokers' perceptions about the availability of tobacco and the role availability may play in tobacco consumption and quitting attempts in Australia. The study comprised two parts: Part A involved mapping retail tobacco outlets in the Hunter Region of NSW, Australia. Part B involved a statewide telephone survey of 539 current smokers aged 18 years and over in NSW. Part A identified 1270 retail tobacco outlets, giving a density of one outlet per 384 persons aged over 15 years, or one outlet per 77 smokers. Associations between socioeconomic status of areas and retail availability of tobacco were not found. Of the survey respondents in Part B, 87.5% indicated that they would be within walking distance of a retail tobacco outlet during their daily activities. Those who were younger, male and single were more likely to purchase tobacco at convenience-type outlets. We therefore conclude that some groups of smokers appear vulnerable to the availability of tobacco and a reduction in the availability of tobacco is likely to benefit smokers who wish to quit.

Defining research priorities for pancreatic cancer in Australia: results of a consensus development process.

INTRODUCTION: Pancreatic cancer (PC) is the sixth leading cause of cancer death in Australia and the fourth in the United States, yet research in PC is lagging behind that in other cancers associated with a high disease burden. In the absence of agreed processes to reliably identify research areas which can deliver significant advances in PC research, the Cancer Council NSW established a strategic partnership with the NSW Pancreatic Cancer Network to define critical research issues and opportunities that could accelerate progress in this field in Australia. MATERIALS AND METHODS: The process consisted of five distinct stages: a literature review on recent progress in PC research, semi-structured expert interviews, a Delphi process, consumer focus groups, and a nominal group process. Information collected at each step informed the development of subsequent stages. RESULTS: The results from these steps were refined by the nominal group into a set of seven specific pancreatic cancer research goals. The goals were disseminated and led to a new funding scheme for key PC research priorities. DISCUSSION: This prioritisation exercise provided a much needed "road map" for research prioritisation in PC and served as a checklist to researchers applying for PC research grants to confirm how their research can contribute towards accelerating progress in PC research in Australia.

A 'Catch Up' Plan for radiotherapy in New South Wales to 2012.

In New South Wales (NSW) from 1996 to 2006, only 34-37% of newly diagnosed cancer patients were treated with radiotherapy instead of the 50% proposed by NSW Health in Radiotherapy Plans released in 1991, 1995 and 2003. As a consequence, over 50 000 cancer patients were not treated and has resulted in the estimated premature death of over 8000 patients and over 40 000 years of life lost. In 2008, there were 42 linear accelerators in NSW rather than the 62 recommended. Based on cancer incidence projections, NSW will require 69 linear accelerators in 2012--a shortfall of 27 linear accelerators. Already 15 linear accelerators have been approved. NSW Health has funding for seven extra linear accelerators, and eight extra linear accelerators are to be funded by the private sector. To make up the shortfall, a 'Catch Up' Plan is proposed for an additional 12 linear accelerators by the end of fiscal year 2012. This is estimated to cost $200 million over 4 years for one-off establishment costs for buildings and equipment plus $50 million per year for recurrent operating costs such as staff salaries. The 'Catch Up' Plan will create five new departments of radiation oncology in country hospitals and three new departments in metropolitan hospitals. These will be in addition to those already approved by NSW Health and will markedly improve access for treatment and result in an improvement in cancer survival. This significant increase in departments and equipment can only be achieved by the creation of an NSW Radiotherapy Taskforce similar to that proposed in the Baume report of 2002, 'A vision for radiotherapy'. Even if the 'Catch Up' Plan bridges the gap in service provision, forward planning beyond 2012 should commence immediately as 76 linear accelerators will be required for NSW in 2015 and 81 linear accelerators in 2017.

Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening.

BACKGROUND/AIMS: In Australia, Asian-born populations are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. We therefore, modelled the consequences of different management strategies for chronic hepatitis B (CHB) in Asian-born adults aged > or = 35 years. METHODS: A Markov model compared (1) enhanced surveillance for HCC alone (HCC surveillance), or (2) enhanced HCC surveillance coupled with CHB treatment (HCC prevention) to the current practice, of low CHB treatment uptake. Patients were stratified and managed according to risk categories, based upon hepatitis B virus (HBV) viral load and alanine aminotransferase (ALT) levels. We measured costs, health outcomes [cases of HCC and deaths averted, quality-adjusted life-years (QALYs) gained] and incremental cost-effectiveness ratios (ICERs). RESULTS: HCC surveillance would cost on average AU$8479 per person, compared to AU$2632 with current clinical practice and result in a gain of 0.014 QALYs (AU$401,516/QALY gained). A HCC prevention strategy would cost on average AU$14,600 per person, result in 0.923 QALYs gained (AU$12,956/QALY gained), reduce cases of cirrhosis by 52%, HCC diagnoses by 47% and CHB-related deaths by 56%, compared to current practice. CONCLUSIONS: HCC prevention appears to be a cost-effective public health strategy in at-risk populations in Australia and is preferable to HCC surveillance as a cancer control strategy.

Preventing primary liver cancer: how well are we faring towards a national hepatitis B strategy?

Worldwide, over 80% of primary liver cancers are attributable to chronic infection with hepatitis B or C virus. Over the past two decades, primary liver cancer incidence rates have been consistently rising in Australia. In New South Wales, the standardised incidence ratios for primary liver cancer in males born in Vietnam, Hong Kong and Macau, Korea, Indonesia and China and in females born in Vietnam and China are 6-12 times those in Australian-born populations. The incidence of liver cancer is likely to continue to increase unless a coordinated approach to disease control can be developed. Effective programs for chronic hepatitis B management need to link prevention, treatment and care, and enhance opportunities for research and surveillance activities. The evidence that suppression of hepatitis B virus replication could limit disease progression needs to inform the development of a public health response. Lessons learned in the development of the National Hepatitis C Strategy and the experience of international hepatitis B control programs need to inform this process.

From inclusion to independence--training consumers to review research.

Health and medical research invariably impacts on the lives of everyday people. Organisations in the developed world are increasingly involving the public in health research projects, and research governance structures and processes. The form the involvement takes varies, as does the level of involvement, from individuals, to groups, to the wider community. Lay community members can be trained to independently review health and medical research, and wider societal involvement in funding decisions, can be effectively fostered. The theoretical foundation, design and development of a task based consumer-training program, including a number of enabling factors to support the success of such training are presented. This work is likely to be of value to those planning to train consumers in technical or complex areas.

Regulation for chronic disease control: the pathfinder role of tobacco.

Regulation for health in the modern era has its foundations in the English Public Health Act of 1848. Early legislation was concerned with controlling environmental causes of disease. However, the focus on regulation today within health departments has diminished, displaced by a focus on services and related programs. The regulatory debate is now centred on what degree of protection, or safety margin, is required, and how regulatory efficiency may be improved. The example of tobacco control is reviewed to show how regulation can play a large role in chronic disease control, and consideration given to how regulatory tools could be further diversified and regulatory effectiveness improved.

Beyond scientific rigour: funding cancer research of public value.

OBJECTIVE: To identify the values deemed by cancer consumers and community members to be important in judging research, and develop an appraisal instrument for the inclusion of consumer and community values in cancer research funding decisions in an independent review process. BACKGROUND: Improvement in the level and quality of consumer involvement in research processes is becoming increasingly recognised as an important area of development in research governance. It was identified that while the current practice of selecting research based on scientific merit satisfies the need to fund research with the best scientific quality and potential for success, this may not necessarily satisfy all the needs and expectations of cancer consumers and the wider community. METHODS: A research team was established to undertake the qualitative study. A combination of focus groups and semi-structured in-depth telephone interviews were conducted to collect and verify information about the values held by cancer consumers and the wider community with regard to research. RESULTS: Consumer review criteria to guide consumers in judging the value of research, optimal rating scales to use with these criteria and views on how consumer needs should be incorporated into the process of judging and allocating research grants (e.g. the relative weight that should be given to scientific and consumer review) have been formally identified by this research. CONCLUSIONS: The findings of this study clarify consumer and community values regarding cancer research funding and offer a means to evaluate research that address these values.