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146 result(s) for "Caruana, Michael"
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Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020–99: a modelling study
Cervical screening and human papillomavirus (HPV) vaccination have been implemented in most high-income countries; however, coverage is low in low-income and middle-income countries (LMICs). In 2018, the Director-General of WHO announced a call to action for the elimination of cervical cancer as a public health problem. WHO has called for global action to scale-up vaccination, screening, and treatment of precancer, early detection and prompt treatment of early invasive cancers, and palliative care. An elimination threshold in terms of cervical cancer incidence has not yet been defined, but an absolute rate of cervical cancer incidence could be chosen for such a threshold. In this study, we aimed to quantify the potential cumulative effect of scaled up global vaccination and screening coverage on the number of cervical cancer cases averted over the 50 years from 2020 to 2069, and to predict outcomes beyond 2070 to identify the earliest years by which cervical cancer rates could drop below two absolute levels that could be considered as possible elimination thresholds—the rare cancer threshold (six new cases per 100 000 women per year, which has been observed in only a few countries), and a lower threshold of four new cases per 100 000 women per year. In this statistical trends analysis and modelling study, we did a statistical analysis of existing trends in cervical cancer worldwide using high-quality cancer registry data included in the Cancer Incidence in Five Continents series published by the International Agency for Research on Cancer. We then used a comprehensive and extensively validated simulation platform, Policy1-Cervix, to do a dynamic multicohort modelled analysis of the impact of potential scale-up scenarios for cervical cancer prevention, in order to predict the future incidence rates and burden of cervical cancer. Data are presented globally, by Human Development Index (HDI) category, and at the individual country level. In the absence of further intervention, there would be 44·4 million cervical cancer cases diagnosed globally over the period 2020–69, with almost two-thirds of cases occurring in low-HDI or medium-HDI countries. Rapid vaccination scale-up to 80–100% coverage globally by 2020 with a broad-spectrum HPV vaccine could avert 6·7–7·7 million cases in this period, but more than half of these cases will be averted after 2060. Implementation of HPV-based screening twice per lifetime at age 35 years and 45 years in all LMICs with 70% coverage globally will bring forward the effects of prevention and avert a total of 12·5–13·4 million cases in the next 50 years. Rapid scale-up of combined high-coverage screening and vaccination from 2020 onwards would result in average annual cervical cancer incidence declining to less than six new cases per 100 000 individuals by 2045–49 for very-high-HDI countries, 2055–59 for high-HDI countries, 2065–69 for medium-HDI countries, and 2085–89 for low-HDI countries, and to less than four cases per 100 000 by 2055–59 for very-high-HDI countries, 2065–69 for high-HDI countries, 2070–79 for medium-HDI countries, and 2090–2100 or beyond for low-HDI countries. However, rates of less than four new cases per 100 000 would not be achieved in all individual low-HDI countries by the end of the century. If delivery of vaccination and screening is more gradually scaled up over the period 2020–50 (eg, 20–45% vaccination coverage and 25–70% once-per-lifetime screening coverage by 2030, increasing to 40–90% vaccination coverage and 90% once-per-lifetime screening coverage by 2050, when considered as average coverage rates across HDI categories), end of the century incidence rates will be reduced by a lesser amount. In this scenario, average cervical cancer incidence rates will decline to 0·8 cases per 100 000 for very-high-HDI countries, 1·3 per 100 000 for high-HDI countries, 4·4 per 100 000 for medium-HDI countries, and 14 per 100 000 for low-HDI countries, by the end of the century. More than 44 million women will be diagnosed with cervical cancer in the next 50 years if primary and secondary prevention programmes are not implemented in LMICs. If high coverage vaccination can be implemented quickly, a substantial effect on the burden of disease will be seen after three to four decades, but nearer-term impact will require delivery of cervical screening to older cohorts who will not benefit from HPV vaccination. Widespread coverage of both HPV vaccination and cervical screening from 2020 onwards has the potential to avert up to 12·5–13·4 million cervical cancer cases by 2069, and could achieve average cervical cancer incidence of around four per 100 000 women per year or less, for all country HDI categories, by the end of the century. A draft global strategy to accelerate cervical cancer elimination, with goals and targets for the period 2020–30, will be considered at the World Health Assembly in 2020. The findings presented here have helped inform initial discussions of elimination targets, and ongoing comparative modelling with other groups is supporting the development of the final goals and targets for cervical cancer elimination. National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control (C4; APP1135172).
Prolonged febrile illness following first dose of ChAdOx1
A woman in her 40s, with a known history of fibromyalgia, presented with high-grade fever and constitutional symptoms occurring 5 days following vaccination with Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1). Her inflammatory markers and neutrophil count were found to be elevated and as such, she was started on antibiotics. Despite treatment, markers remained elevated and temperature spikes persisted for another 4 weeks before these symptoms subsided, and her blood tests normalised. All investigations taken in the interim were negative, with no source being identified for the fever. As a result, a positron emission tomography scan was performed to attempt to localise the source of these symptoms. This revealed low-to-moderate grade lymph node tracer uptake above and below the diaphragm most pervasive in the right axilla, with uptake in the right arm corresponding with the site of vaccination.
Acquired angioedema: an unusual presentation of haematological malignancy
A previously healthy man in his 60s being worked up for splenomegaly presented to the emergency department with recurrent episodes of angioedema. Each episode was attributed to a precipitating cause, and consequently, the predisposing C1 esterase inhibitor (C1-INH) deficiency remained undiagnosed until the third presentation. The aetiology of acquired C1-INH deficiency would be primarily obscure and require further investigations to identify. A clonal B cell population was finally isolated by flow cytometry after multiple repeat marrow samples, and a diagnosis of splenic marginal zone lymphoma was subsequently reached. Response to single-agent rituximab was observed with resolution of splenomegaly, disappearance of the antibody and restoration of C1-INH levels.
Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial
Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia's HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%-77%). Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25-64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology ('LBC screening'), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types ('HPV+LBC triage'), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types ('HPV+DS triage'). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%-3.9%]) and 1/995 (0.1% [95% CI 0.0%-0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%-4.7%]) and 20/1,992 (1.0% [95% CI 0.6%-1.5%]); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%-4.9%]) and 24/2,008 (1.2% [95% CI 0.8%-1.6%]) (p = 0.09 for difference in referral rate in LBC versus all HPV-screened women; p = 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with p = 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women's vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available. In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%-44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations. Australian New Zealand Clinical Trials Registry ACTRN12613001207707.
COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study
COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020–2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.
Fifty-year forecasts of daily smoking prevalence: can Australia reach 5% by 2030?
ObjectiveTo compare 50-year forecasts of Australian tobacco smoking rates in relation to trends in smoking initiation and cessation and in relation to a national target of ≤5% adult daily prevalence by 2030.MethodsA compartmental model of Australian population daily smoking, calibrated to the observed smoking status of 229 523 participants aged 20–99 years in 26 surveys (1962–2016) by age, sex and birth year (1910–1996), estimated smoking prevalence to 2066 using Australian Bureau of Statistics 50-year population predictions. Prevalence forecasts were compared across scenarios in which smoking initiation and cessation trends from 2017 were continued, kept constant or reversed.ResultsAt the end of the observation period in 2016, model-estimated daily smoking prevalence was 13.7% (90% equal-tailed interval (EI) 13.4%–14.0%). When smoking initiation and cessation rates were held constant, daily smoking prevalence reached 5.2% (90% EI 4.9%–5.5%) after 50 years, in 2066. When initiation and cessation rates continued their trajectory downwards and upwards, respectively, daily smoking prevalence reached 5% by 2039 (90% EI 2037–2041). The greatest progress towards the 5% goal came from eliminating initiation among younger cohorts, with the target met by 2037 (90% EI 2036–2038) in the most optimistic scenario. Conversely, if initiation and cessation rates reversed to 2007 levels, estimated prevalence was 9.1% (90% EI 8.8%–9.4%) in 2066.ConclusionA 5% adult daily smoking prevalence target cannot be achieved by the year 2030 based on current trends. Urgent investment in concerted strategies that prevent smoking initiation and facilitate cessation is necessary to achieve 5% prevalence by 2030.
Trends in colon and rectal cancer mortality in Australia from 1972 to 2015 and associated projections to 2040
Previously published sub-site Australian projections for colon and rectal cancers to 2035 using the World Health Organization’s mortality database sourced from the Australian Bureau of Statistics (ABS) predicted mortality rate decreases for colon cancer and increases for rectal cancer. There are complexities related to the interpretation of ABS’s Australian colon and rectal cancer mortality rates, which could lead to possible inaccuracies in mortality rates for these sub-sites. The largest Australian population-wide registry, New South Wales Cancer Registry (NSWCR), compares routinely-reported causes of death with the recorded medical history from multiple data sources. Therefore, this study used the NSWCR data to project mortality rates for colon and rectal cancers separately to 2040 in Australia. The mortality rates for colon cancer are projected to continuously decline over the period 2015–2040, from 7.0 to 4.7 per 100,000 males, and from 5.3 to 3.2 per 100,000 females. Similar decreasing trends in mortality rates for rectal cancer were projected over the period 2015–2040, from 4.9 to 3.7 per 100,000 males, and from 2.6 to 2.3 per 100,000 females. These projections provide benchmark estimates for the colorectal cancer burden in Australia against which the effectiveness of cancer control interventions can be measured.
Birth-cohort estimates of smoking initiation and prevalence in 20th century Australia: Synthesis of data from 33 surveys and 385,810 participants
The aim of our study was to quantify sex-specific patterns of smoking prevalence and initiation in 10-year birth cohorts from 1910 to 1989 in Australia. We combined individual data of 385,810 participants from 33 cross-sectional surveys conducted between 1962 and 2018. We found that age-specific smoking prevalence varied considerably between men and women within birth cohorts born before 1960. The largest difference was observed in the earliest cohort (1910–1919), with up to 37.7% point greater proportion of current smokers in men than in women. In subsequent cohorts, the proportion decreased among men, but increased among women, until there was no more than 7.4% point difference in the 1960–69 birth cohort. In the 1970–79 and 1980–89 cohorts, smoking among men marginally increased, but the proportion was at most ~11.0% points higher than women. Our analysis of initiation indicated that many women born before the 1930s who smoked commenced smoking after age 25 years (e.g., ~27% born in 1910–19); compared to at most 8% of men in any birth cohort. The earliest birth cohort (1910–1919) had the greatest difference in age at initiation between sexes; 26.6 years in women versus 19.0 in men. In later cohorts, male and female smokers initiated increasingly earlier, converging in the 1960–69 cohort (17.6 and 17.8 years, respectively). While 22.9% of men and 8.4% of women initiated smoking aged < = 15 in the 1910–1919 cohort, in the latest cohort (1980–89) the reverse was true (21.4% and 28.8% for men and women, respectively). Marked differences in smoking prevalence and age at initiation existed between birth cohorts of Australian men and women born before 1960; after this, sex-specific trends in prevalence and initiation were similar. Understanding these patterns may inform the evaluation of tobacco control policies and the targeting of potential interventions for exposed populations such as lung cancer screening.
Statistical projection methods for lung cancer incidence and mortality: a systematic review
ObjectivesTo identify and summarise all studies using statistical methods to project lung cancer incidence or mortality rates more than 5 years into the future.Study typeSystematic review.MethodsWe performed a systematic literature search in multiple electronic databases to identify studies published from 1 January 1988 to 14 August 2018, which used statistical methods to project lung cancer incidence and/or mortality rates. Reference lists of relevant articles were checked for additional potentially relevant articles. We developed an organisational framework to classify methods into groups according to the type of data and the statistical models used. Included studies were critically appraised using prespecified criteria.ResultsOne hundred and one studies met the inclusion criteria; six studies used more than one statistical method. The number of studies reporting statistical projections for lung cancer increased substantially over time. Eighty-eight studies used projection methods, which did not incorporate data on smoking in the population, and 16 studies used a method which did incorporate data on smoking. Age–period–cohort models (44 studies) were the most commonly used methods, followed by other generalised linear models (35 studies). The majority of models were developed using observed rates for more than 10 years and used data that were considered to be good quality. A quarter of studies provided comparisons of fitted and observed rates. While validation by withholding the most recent observed data from the model and then comparing the projected and observed rates for the most recent period provides important information on the model’s performance, only 12 studies reported doing this.ConclusionThis systematic review provides an up-to-date summary of the statistical methods used in published lung cancer incidence or mortality projections. The assessment of the strengths of existing methods will help researchers to better apply and develop statistical methods for projecting lung cancer rates. Some of the common methods described in this review can be applied to the projection of rates for other cancer types or other non-infectious diseases.
A systematic review of microsimulation models for skin cancer
Background Simulation modelling can assist with health care decision making. To inform the development and improvement of skin cancer focussed microsimulation models, we conducted a systematic review and narrative synthesis of published skin cancer models to assess the structure, parameterisation, and assumptions. Methods The electronic databases OVIDMedline including Embase and the Cost-Effectiveness Analysis (CEA) Registry were searched up to 7 May 2025. Studies that included microsimulation of individuals who developed or had skin cancer were eligible for inclusion. No restrictions on publication date or language were applied. The outcomes of interest were the purpose of the models, characteristics of the models and applicability for modelling skin cancer screening. Results Twenty-two models were identified from the systematic review. Nineteen papers modelled melanoma, and two papers modelled keratinocyte or non-melanoma skin cancer, and one paper modelled both melanoma and keratinocyte cancer. The models were developed to assess treatment strategies ( n  = 10), skin cancer screening programs ( n  = 7), diagnostic techniques ( n  = 3), post-diagnosis surveillance ( n  = 3), preventative interventions ( n  = 1) and time to treatment ( n  = 1), with three models reporting dual aims. There was substantial variation in the simulation of the natural history of melanoma between models, with more recent models having separate natural history and clinical modules. The quality was assessed using the Quality Assessment Reporting for Microsimulation Models (QARMM) checklist and the majority of models were assessed to be of moderate quality. Limitations from these models included assuming an average tumour behaviour and constant melanoma development and progression over time. Data availability was also noted as a limitation for some models. Conclusions Most microsimulation models related to skin cancer have focused on late-stage treatment strategies. Tumour characteristics, apart from stage at diagnosis, were not accounted for in most models. PROSPERO registration number CRD42024504250.