Search

Introduction: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex‐specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. Methods: HCV notifications in New South Wales, Australia (1995–2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016–2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18–44), including those with recent drug dependence. Results: Among 57,467 people with evidence of chronic HCV in the DAA era (2016–2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18–44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Conclusion: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination. [ABSTRACT FROM AUTHOR]

Background People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. Methods We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016–December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. Results Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. Conclusions Among people who have evidence of recent drug dependence, frequent hospitalization—particularly mental health, drug, and alcohol admissions—presents an opportunity for engagement in HCV care. [ABSTRACT FROM AUTHOR]

• Prior to the introduction of DAA therapy, the disease burden of HCV was rising in New South Wales. • DAA scale-up has had a major population-level impact on HCV morbidity and mortality. • The World Health Organization has set a 65% HCV mortality reduction target by 2030. • To achieve this target, enhanced efforts are required to continue DAA scale-up. • In the DAA era, the impact of heavy alcohol use on liver disease should be monitored. Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001–2014) and DAA therapy (2015–2017) eras in New South Wales, Australia. HCV notifications (1993–2016) were linked to hospital admissions (2001–2017) and mortality (1995–2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04–1.05], 1.08 [95% CI 1.07–1.08], 1.07 [95% CI 1.06–1.07], and 1.05 [95% CI 1.04–1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95–0.99] and 0.96 [95% CI 0.94–0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97–1.03] and 1.01 [95% CI 1.00–1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14–3.58). In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported an excess burden of cancer and mortality in populations with chronic hepatitis B (HBV) or C (HCV), but there are limited data comparing hospitalization rates. In this study, we compared hospitalization rates for all causes and viral liver disease in people notified with HBV or HCV in New South Wales (NSW), Australia. Methods: HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends. Results: The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (P < 0.001). Conclusion: Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend. [ABSTRACT FROM AUTHOR]

Aims The aims of this study were to: examine the number and characteristics of patients entering and re-entering opioid replacement treatment between 1985 and 2006, to examine select demographic and treatment correlates of leaving treatment between 1985 and 2000, and to compare retention rates in methadone and buprenorphine maintenance treatment from 2001 to 2006. Design A retrospective cohort study using register data from the Pharmaceutical Drugs of Addiction System. Setting Opioid substitution treatment in New South Wales (NSW), Australia. Participants A total of n = 42 690 individuals prescribed opioid replacement treatment between 1985 and 2006 in NSW. Measurements Client characteristics over time, retention in days in first treatment episode, number of episodes of treatment and proportion switching medication. Findings Overall, younger individuals were significantly more likely to leave their first treatment episode than older individuals. In 2001–06, after controlling for age, sex and first administration point, the hazard of leaving treatment was 1.9 times for those on buprenorphine relative to those on methadone. Retention in treatment varied somewhat across historical time, with those entering during 1995–2000 more likely to leave at an earlier stage than those who entered before that time. Conclusions Retention in treatment appears to fluctuate in inverse proportion to the availability of heroin. Individuals in contemporary treatment are older users with a lengthy treatment history. This study has provided population-level evidence to suggest that retention in methadone and buprenorphine differ in routine clinical practice. Future work might investigate ways in which patient adherence and retention may be improved. [ABSTRACT FROM AUTHOR]

Background and Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV-related HCC survival. Methods: Data on HBV-related HCC cases was obtained from a community-based linkage study. HCC cases notified to the New South Wales (NSW) Central Cancer Registry (CCR) during the period 1994–2002 were linked to HBV notifications from the NSW Health Department. Age, sex, country of birth, year of diagnosis, tumor stage were extracted from the CCR database. Survival analysis was conducted to determine median survival and identify predictors of survival. Results: Over the 9-year study period, 278 HCC cases were linked to chronic HBV infection. The majority of cases were male (83.5%) and overseas-born (93.6%); Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was 15.0 months. HCC survival was poorer among older age groups ( P < 0.0001), and among cases with regional spread (hazard ratio, 3.23; 95% confidence interval, 1.83–5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence interval, 2.44–6.08; P < 0.0001). Sex, region of birth and study period (1994–1997 vs 1998–2002) were not associated with HCC survival. Conclusion: The vast majority of HBV-related HCC were overseas-born, however, region of birth was unrelated to HCC survival. The continued extremely poor HCC survival, including lack of improvement in HCC survival in more recent years, suggests low uptake of HCC screening programs. Public health strategies including early diagnosis and appropriate referral for antiviral therapy assessment and increased HCC screening among high-risk populations are required to reduce HCC incidence and improve HCC survival. [ABSTRACT FROM AUTHOR]

Summary Background Hepatitis B and hepatitis C virus infections are common causes of death related to liver disease. In this large study, we aimed to investigate all cause mortality of the viruses in a community-based setting. Methods In the study population, 39 109 people had hepatitis B, 75 834 had hepatitis C, and 2604 had hepatitis B and hepatitis C co-infection, notified to the New South Wales state health department, Australia, between 1990 and 2002. Their data were probabilistically linked to the National Death Index. Standardised mortality ratios for all causes of death were calculated and adjusted for age, sex, and calendar year. Results The number of deaths identified by the linkage were 1233 (3·2%) for hepatitis B, 4008 (5·3)% for hepatitis C, and 186 (7·1)% for hepatitis B and C co-infection. Raised risk of liver-related death (standardised mortality ratios 12·2, 95% CI 10·7-13·9; 16·8, 15·4-18·3, and 32·9, 23·1-46·7, for hepatitis B, hepatitis C, and hepatitis B and C co-infected patients, respectively) and drug-induced death (1·4, 1·0-2·0; 19·3, 18·1-20·5; and 24·7, 18·2-33·5, respectively) were detected. In people with hepatitis C, raised risk of dying from drug-related causes was significantly greater than from liver-related causes (p=0·012), with the greatest excess risk in women aged 15-24 years (56·9, 39·2-79·9). Interpretation All groups had increased risk of liver-related death compared with the standard population, with the greatest excess in people diagnosed with hepatitis B and hepatitis C co-infection. Our data highlight that young people with hepatitis C and with co-infection face a higher mortality risk from continued drug use than from their infection, whereas the main cause of hepatitis B death was liver related. [ABSTRACT FROM AUTHOR]

High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98). These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced. • People who inject drugs are a key population for hepatitis C elimination. • Australia has provided universal access to direct-acting antiviral therapy since 2016. • Data linkage was used to assess population-level direct-acting antiviral uptake. • Those with evidence of recent drug dependence had the highest treatment uptake. • Despite higher direct-acting antiviral uptake among those with recent drug dependence, gaps remain. [ABSTRACT FROM AUTHOR]

Background & Aims: Statistics are available about hepatitis C (HCV)-related transplants, mortality and cancer risk but little is known about morbidity in the earlier stages of infection. We examined condition specific (principal diagnosis) and overall hospitalization rates for the cohort of individuals notified with hepatitis C in New South Wales (NSW), Australia. Methods: HCV notifications in NSW were linked to their hospital records (available for July 2000 to June 2006), HIV and hepatitis B notifications, and death records. Cases co-infected with HIV or hepatitis B were excluded. Hospitalization rates by person-years of observation were calculated and compared with those expected using rates for the NSW population to calculate standardized hospitalization ratios (SHRs). Results: Patterns of admission were generally similar to the NSW population, with the highest rates in the elderly. However, rates were 42% higher than expected overall and significantly increased in ages 15–64years. The greatest was excess in 15–19year olds (SHR 3.8, 95% CI 3.4–4.2), especially females (SHR 4.5, 95% CI 4.1–4.9). Lifestyle factors accounted for the highest absolute and relative rates in young adults while liver disease contributed the greatest burden in older adults. Illicit drug-related conditions accounted for 9% of admissions (SHR 16.1, 95% CI 15.7–16.6) while alcohol and liver-related conditions each accounted for 5% (SHRs 5.1, 95% CI 4.9–5.4 and 15.7, 95% CI 15.0–16.4, respectively). Conclusions: Our findings highlight the need for strategies to minimize lifestyle-related harms, including alcohol consumption, and to improve HCV treatment uptake, in order to reduce morbidity in people with HCV infection. [Copyright &y& Elsevier]

Abstract: Background: The small size of previous studies of mortality in opioid dependent people has prevented an assessment of the extent to which elevated mortality risks are consistent across time, clinical and/or patient groups. The current study examines reductions in mortality related to treatment in an entire treatment population. Methods: Data from the New South Wales (NSW) Pharmaceutical Drugs of Addiction System, recording every “authority to dispense” methadone or buprenorphine as opioid replacement therapy, 1985–2006, was linked with data from the National Deaths Index, a record of all deaths in Australia. Crude mortality rates and standardized mortality ratios were calculated according to age, sex, calendar year, period in- or out-of-treatment, medication type, previous treatment exposure and cause of death. Results: Mortality among 42,676 people entering opioid pharmacotherapy was elevated compared to age and sex peers. Drug overdose and trauma were the major contributors. Mortality was higher out of treatment, particularly during the first weeks, and it was elevated during induction onto methadone but not buprenorphine. Mortality during these risky periods changed across time and treatment episodes. Overall, mortality was similarly reduced (compared to out-of-treatment) whether patients were receiving methadone or buprenorphine. It was estimated that the program produced a 29% reduction in mortality across the entire cohort. Conclusions: Mortality among treatment-seeking opioid-dependent persons is dynamic across time, patient and treatment variables. The comparative reduction in mortality during buprenorphine induction may be offset by the increased risk of longer out-of-treatment time periods. Despite periods of elevated risk, this large-scale provision of pharmacotherapy is estimated to have resulted in significant reductions in mortality. [Copyright &y& Elsevier]

Background: Financial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT), to our knowledge. This trial aimed to determine whether chlamydia testing in general practice is sustained when financial incentives and/or audit/feedback are removed., Methods and Findings: We undertook a 2 × 2 factorial cluster RCT in 60 general practices in 4 Australian states targeting 49,525 patients aged 16-29 years for annual chlamydia testing. Clinics were recruited between July 2014 and September 2015 and were followed for up to 2 years or until 31 December 2016. Clinics were eligible if they were in the intervention group of a previous cluster RCT where general practitioners (GPs) received financial incentives (AU$5-AU$8) for each chlamydia test and quarterly audit/feedback reports of their chlamydia testing rates. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained (group A), audit/feedback removed but incentives retained (group B), both removed (group C), or both retained (group D). The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients, where the numerator was the number who had at least 1 chlamydia test within 12 months and the denominator was the number who had at least 1 consultation during the same 12 months. We undertook a factorial analysis in which we investigated the effects of removal versus retention of incentives (groups A + C versus groups B + D) and the effects of removal versus retention of audit/feedback (group B + C versus groups A + D) separately. Of 60 clinics, 59 were randomised and 55 (91.7%) provided data (group A: 15 clinics, 11,196 patients; group B: 14, 11,944; group C: 13, 11,566; group D: 13, 14,819). Annual testing decreased from 20.2% to 11.7% (difference -8.8%; 95% CI -10.5% to -7.0%) in clinics with incentives removed and decreased from 20.6% to 14.3% (difference -7.1%; 95% CI -9.6% to -4.7%) where incentives were retained. The adjusted absolute difference in treatment effect was -0.9% (95% CI -3.5% to 1.7%; p = 0.2267). Annual testing decreased from 21.0% to 11.6% (difference -9.5%; 95% CI -11.7% to -7.4%) in clinics where audit/feedback was removed and decreased from 19.9% to 14.5% (difference -6.4%; 95% CI -8.6% to -4.2%) where audit/feedback was retained. The adjusted absolute difference in treatment effect was -2.6% (95% CI -5.4% to -0.1%; p = 0.0336). Study limitations included an unexpected reduction in testing across all groups impacting statistical power, loss of 4 clinics after randomisation, and inclusion of rural clinics only., Conclusions: Audit/feedback is more effective than financial incentives of AU$5-AU$8 per chlamydia test at sustaining GP chlamydia testing practices over time in Australian general practice., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12614000595617., Competing Interests: All authors have completed the ICMJE uniform disclosure form. I have read the journal’s policy and the authors have the following competing interests: ML has received research grants to his institution from Gilead Sciences, Janssen-Cilag and ViiV Healthcare; NL is a member of the Editorial Board of PLOS Medicine.

Background: This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia., Methods: Notifications 1993-2012 were linked to cause-specific mortality records 1993-2013., Results: Among 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P < 0.001); however, HCV-related rates remained stable (0.2 to 0.3 per 100 PY, P = 0.619). In adjusted analyses, older age was the strongest predictor of liver-related mortality [birth earlier than 1945, HBV adjusted hazard ratio (aHR) 28.1, 95% CI 21.0, 37.5 and; HCV aHR 31.9, 95% CI 26.8, 37.9], followed by history of alcohol-use disorder (HBV aHR 7.0, 95% CI 5.5, 8.8 and; HCV aHR 8.3, 95% CI 7.6, 9.1)., Conclusions: Declining HBV-related liver mortality rates and stable burden suggest an impact of improved antiviral therapy efficacy and uptake. In contrast, the impact of interferon-containing HCV treatment programs on liver-related mortality individual-level risk and population-level burden has been limited. These findings also highlight the importance of HBV/HCV public health interventions that incorporate increased antiviral therapy uptake, and action on health risk behaviors.

Background & Aims: People living with hepatitis C virus (HCV) are at increased risk of all-cause and liver-related mortality, although successful treatment has been shown to reduce this risk. The aim of this study was to provide baseline data on trends in cause-specific mortality and to establish an international surveillance system for evaluating the population level impact of HCV treatments., Methods: Population level HCV diagnosis databases from Scotland (1997-2010), Australia (New South Wales [NSW]) (1997-2006), and Canada (British Columbia [BC]) (1997-2003) were linked to corresponding death registries using record linkage. For each region, age-adjusted cause-specific mortality rates were calculated, and trends in annual age-adjusted liver-related mortality were plotted., Results: Of 105,138 individuals diagnosed with HCV (21,810 in Scotland, 58,484 in NSW, and 24,844 in BC), there were 7275 deaths (2572 in Scotland, 2655 in NSW, and 2048 in BC). Liver-related deaths accounted for 26% of deaths in Scotland, 21% in NSW, and 22% in BC. Temporal trends in age-adjusted liver related mortality were stable in Scotland (males p=0.4; females p=0.2) and NSW (males p=0.9; females p=0.9), while there was an increase in BC (males p=0.002; females p=0.04)., Conclusions: The risk of liver-related mortality after a diagnosis of HCV has remained stable or increased over time across three regions with well-established diagnosis databases, highlighting that HCV treatment programmes to-date have had minimal impact on population level HCV-related liver disease. With more effective therapies on the horizon, and greater uptake of treatment anticipated, the potential of future therapeutic strategies to reduce HCV-related mortality is considerable., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To estimate the overall and cause specific mortality of Aboriginal offenders in New South Wales (NSW), Australia., Methods: The study cohort consisted of all Aboriginal men and women aged 18 years and older who had experienced full-time imprisonment in NSW between 1 January 1988 and 31 December 2002. Their data were linked probabilistically to the Australian National Death Index to obtain information on death. Standardised mortality ratios were calculated for all causes of death and adjusted for age, sex, and calendar year., Results: The cohort comprised 7,980 men and 1,373 women with 75,801 person years of observation. During a median follow-up period of 8.3 years, 485 men and 73 women died, giving an overall mortality rate of 733 and 755 deaths per 100,000 person-years. The risk of death in men was 4.8 (95% CI: 4.4-5.3) times and among women 12.6 (95% CI: 10.0-15.8) times that of the NSW residents, with a markedly elevated risk for almost all conditions. The leading cause of death was cardiovascular disease in men (112 deaths, 23%) and mental and behavioural disorders (17 deaths, 23%) in women. The risk of death was greatest following release from prison., Conclusions and Implications: High mortality rates for cardiovascular disease, a preventable and treatable condition, were seen among Aboriginal offenders. Prison has an important role to play in screening marginalised populations for a range of health conditions. This is particularly true for Indigenous offenders., (© 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.)

Objective: To examine cancer mortality in a population-based cohort of opioid-dependent persons., Methods: New South Wales opioid substitution therapy (OST) program registrants from 1985 to 2005 (n=43,789) were probabilistically linked to the National Death Index. Crude and standardised mortality rates and standardised mortality ratios (SMRs) were calculated., Results: The crude cancer mortality rate increased from 4 to 65 deaths per 100,000 person-years (p trend <0.001). Overall, OST registrants were 1.7 times more likely to die of cancer than the general population (SMR 95% CI 1.4-1.9). Site-specific SMRs were significantly elevated for lung cancer (3.6, 95% CI 2.8-4.6), liver cancer (6.9, 95% CI 4.3-10.5), and anogenital cancers (2.8, 95% CI 1.3-5.3), and significantly reduced for breast cancer (0.4, 95% CI 0.1-0.9)., Conclusions: Cancer is an increasingly important cause of death among OST registrants as they live longer with their dependency. The site-specific excess deaths suggest the role of tobacco, alcohol, and infection with hepatitis C and human papillomavirus., Implications: The OST setting may be a useful setting for the delivery of programs aimed at detection of precursor lesions, reducing exposure to established carcinogens, and treatment for those with HCV infection. Such targeted steps are likely to reduce the future cancer burden in this population., (© 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.)

Background & Aims: Chronic hepatitis B (HBV) or C (HCV) virus infection has been associated with increased risk of death, particularly from liver- and drug-related causes. We examined specific causes of death among a population-based cohort of people infected with HBV or HCV to identify areas of excess risk and examine trends in mortality., Methods: HBV and HCV cases notified to the New South Wales (NSW) Health Department between 1992 and 2006 were linked to cause of death data and HIV/AIDS notifications. Mortality rates and standardised mortality ratios (SMRs) were calculated using person time methodology, with NSW population rates used as a comparison., Results: The study cohort comprised 42,480 individuals with HBV mono-infection and 82,034 with HCV mono-infection. HIV co-infection increased the overall mortality rate three to 10-fold compared to mono-infected groups. Liver-related deaths were associated with high excess risk of mortality in both HBV and HCV groups (SMR 10.0, 95% CI 9.0-11.1; 15.8, 95% CI 14.8-16.8). Drug-related deaths among the HCV group also represented an elevated excess risk (SMR 15.4, 95% CI 14.5-16.3). Rates of hepatocellular carcinoma (HCC)-related death remained steady in both groups. A decrease in non-HCC liver-related deaths was seen in the HBV group between 1997 and 2006, but not in the HCV group. After a sharp decrease between 1999 and 2002, drug-related mortality rates in the HCV group have been stable., Conclusions: Improvements in HBV treatment and uptake have most likely reduced non-HCC liver-related mortality. Encouragingly, HCV drug-related mortality remained low compared to pre-2002 levels, likely due to changes in opiate supply, and maintenance or improvement in harm reduction strategies., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To determine risk factors and estimate their population-level contribution to hepatitis C virus (HCV) burden., Methods: Established and potentially modifiable risk factors were estimated using partial population attributable risk (PAR(p)) in a cohort of new injecting drug users (IDUs) in Sydney, Australia., Results: A total of 204 hepatitis C seronegative IDUs were recruited through street-based outreach, methadone clinics and needle and syringe programmes (NSPs) and followed-up at 3-6-monthly intervals. A total of 61 HCV seroconversions were observed during the follow-up [overall incidence rate of 45.8 per 100 person-years (95% confidence interval: 35.6-58.8)]. Overall, five potentially modifiable risk factors (sharing needles/syringes, sharing other injecting equipment, assisted injecting, frequency of injection and not being in drug treatment) accounted for approximately 50% of HCV cases observed., Conclusion: While sharing needles/syringes or other injecting equipment were associated most strongly with increased risk of HCV infection, the PAR(p) associated with these behaviours was relatively modest (12%) because they are relatively low-prevalence behaviours. Our analyses suggest that more HCV infection could be avoided by changing more common, but less strongly associated behaviours such as assisted injecting or daily injecting. Results suggest that to have a very substantial effect on HCV, a range of risk factors need modifying. The most efficient use of scarce resources in reducing HCV infections will require complex balancing between the PAR for a given risk factor(s), the efficacy of interventions to actually modify the risk factor, and the cost of these interventions.

Spatio-temporal clustering of sporadic Creutzfeldt-Jakob disease (sCJD) has been recognized and investigated previously in various global settings including Australia. Generally, despite often extensive investigation, explanations such as point source outbreaks and plausible case-to-case transmission links have not been identified to explain the apparently higher case rates than expected. In the context of national surveillance during the period 1993-2006, an increased number of cases of sCJD were recognized in a circumscribed coastal region of eastern Australia. To assess the significance of this apparent clustering, the Spatial Scan Statistic was used to examine for geographic excess of CJD mortality at spatial and temporal combined, spatial only and temporal only levels. A significant spatial cluster was confirmed, encompassing three contiguous statistical local areas within the state of New South Wales (NSW). Detailed epidemiological analysis did not reveal a plausible cross-over or point source transmission event. Further evaluation prompted the conclusion that vigilant and motivated managing clinicians in this geographically circumscribed area of NSW evinced a sustained higher level of clinical awareness for the broad phenotypic spectrum of CJD with reliable referral of suspect cases for further investigation. In addition, these physicians established and maintained a well-coordinated and active approach to suspect CJD autopsy. This combination of factors translated into a higher intensity of surveillance at approximately twice the rate per population observed in the entire state, culminating in twice the incidence of sCJD at around 2.28 cases/million population/year. The hypothesis that intensity of surveillance for rare disorders can be objectively measured and that this can positively correlate with disease incidence deserves further exploration. It may prove to be an important insight into the varying incidence rates over periods of time within individual nations and between different countries.

Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006., Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts., Results: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community-based surveys in Australia (69-85% and 49-83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small., Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.

Background: Since 1999 there has been an increase in the number of HIV diagnoses in Australia, predominantly among men who have sex with men (MSM), but the magnitude of increase differs between states: approximately 7% rise in New South Wales, approximately 96% rise in Victoria, and approximately 68% rise in Queensland., Methods: Epidemiological, clinical, behavioural and biological data were collated into a mechanistic mathematical model to explore possible reasons for this increase in HIV notifications in MSM. The model was then used to make projections to 2015 under various scenarios., Results: The model suggests that trends in clinical and behavioural parameters, including increases in unprotected anal intercourse, cannot explain the magnitude of the observed rise in HIV notifications, without a substantial increase in a 'transmission-increasing' factor. We suggest that a highly plausible biological factor is an increase in the prevalence of other sexually transmissible infections (STI). It was found that New South Wales required an approximately 2-fold increase in other STI to match the data, Victoria needed an ~11-fold increase, and Queensland required an approximately 9-fold increase. This is consistent with observed trends in Australia for some STI in recent years. Future projections also indicate that the best way to control the current rise in HIV notifications is to reduce the prevalence of other STI and to promote condom use, testing for HIV, and initiation of early treatment in MSM diagnosed during primary infection., Conclusions: Our model can explain the recent rise in HIV notifications with an increase in the prevalence of other STI. This analysis highlights that further investigation into the causes and impact of other STI is warranted in Australia, particularly in Victoria.

Background/aims: Hepatocellular carcinoma (HCC) incidence has increased in Australia in the past 20-30 years. We conducted a community-based linkage study to examine the characteristics of hepatocellular carcinoma with particular reference to hepatitis B and C infections., Methods: Hepatocellular carcinoma cases (n=2,072) notified to the New South Wales (NSW) Central Cancer Registry from 1990 to 2002 were probabilistically linked to HBV and HCV diagnoses notified to NSW Health. Sex, age, year of diagnosis, region of birth, method of diagnosis and spread at diagnosis and survival were compared by linkage group., Results: Hepatocellular carcinoma incidence increased from 1.4/100,000 in 1990 to 2.8/100,000 in 2002. Incidence varied by region of birth (p<0.001), with people born in Vietnam having the highest relative rate compared with those born in Australia (RR=11.7, 95% CI 9.8-13.8). Of the hepatocellular carcinoma records, 15.6%, 12.9% and 0.8% were linked to hepatitis B, hepatitis C and hepatitis B/C co-infection respectively and 70.7% were unlinked. Median age at diagnosis of HCV-related hepatocellular carcinoma varied markedly at 51, 68 and 71 years for Australian, European, and Asian-born groups, respectively (p<0.0001)., Conclusion: Contrasting age distribution of HCV-related HCC by country/region of birth is consistent with divergent patterns of HCV transmission., Implications: These data highlight the increase in HCC in NSW and the divergent populations whose needs in terms of treatment, care and prevention will need to be met.

Objective: Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes. Definitions exist to identify those "at risk." Treatment of HIV infection with highly active antiretroviral therapy can induce severe metabolic complications including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of this study was to report the prevalence of metabolic syndrome in HIV-infected patients and compare insulin resistance and total body, limb, and visceral fat and adipokines in those with and without metabolic syndrome., Research Design and Methods: This was an international cross-sectional study of a well-characterized cohort of 788 HIV-infected adults recruited at 32 centers. Metabolic syndrome prevalence was examined using International Diabetes Federation (IDF) and U.S. National Cholesterol Education Program Adult Treatment Panel III (ATPIII) criteria, relative to body composition (whole-body dual-energy X-ray absorptiometry and abdominal computed tomography), lipids, glycemic parameters, insulin resistance, leptin, adiponectin, and C-reactive protein (CRP)., Results: The prevalence of metabolic syndrome was 14% (n = 114; 83 men) by IDF criteria and 18% (n = 139; 118 men) by ATPIII criteria; the concordance was significant but only moderate (kappa = 0.46, P < 0.0001). Many patients (49%) had at least two features of metabolic syndrome but were not classified as having metabolic syndrome as their waist circumferences or waist-to-hip ratios were in the non-metabolic syndrome range. Metabolic syndrome was more common in those currently receiving protease inhibitors (P = 0.04). Type 2 diabetes prevalence was five- to ninefold higher in those with metabolic syndrome. With IDF criteria, subjects with metabolic syndrome showed disturbances in inflammation and adipokines: they had higher CRP (5.5 +/- 7.0 vs. 3.9 +/- 6.0 mg/l, P < 0.003) and leptin (9 +/- 9 vs. 4 +/- 6 ng/ml, P < 0.0001) and lower adiponectin (12 +/- 8 vs. 15 +/- 10 microg/ml, P < 0.0001) levels. By ATPIII criteria, those with metabolic syndrome had higher leptin (6 +/- 8 ng/ml, P = 0.006) and lower adiponectin (15 +/- 10 vs. 18 +/- 8 microg/ml, P < 0.0001) levels., Conclusions: Metabolic syndrome prevalence in HIV-positive adults was lower than that reported for the general population. Metabolic syndrome was associated with a substantially increased prevalence of type 2 diabetes in this specific cohort. Many subjects without metabolic syndrome had at least two metabolic syndrome components (particularly elevated lipid levels) but did not meet waist circumference or waist-to-hip ratio cutoff metabolic syndrome criteria in this group with high rates of body fat partitioning disturbances.

To assess whether workers at Lucas Heights Science and Technology Centre (LHSTC) had different levels of cancer incidence from the New South Wales (NSW) population in Australia. A retrospective cohort study was undertaken at LHSTC. Data on 7,076 workers employed between 1957-98 were abstracted from personnel, dosimetry, and medical files. An inception cohort was defined which included 4,523 workers in employment between 1972-96 to examine cancer incidence. Cancer registrations in the inception cohort were identified to 1996 through electronic linkage of records with the NSW and the Australian national registers of cancer incidence. All-cancer incidence in workers at LHSTC was 15% below the NSW rates [SIR=0.85; 95% CI=(0.75, 0.95)]. Of 37 specific cancers and groups of cancers examined, statistically significant excesses relative to NSW rates were observed only for pleural cancer incidence [SIR=17.71; 95%=(7.96, 39.43)], and for incidence of cancer of the small intestine [SIR=4.34; 95% CI=(1.40, 13.46)]. This study gives little evidence of an increased risk of cancers associated with radiation exposure in a cohort of nuclear workers in Australia. The observed increase in the risk of cancer of the pleura was probably due to unmeasured exposures, given the lack of an established association with radiation exposure, and the strong link to asbestos exposure. Findings for cancers of the small intestine were based on small numbers and were likely to be due to chance.

Background/aims: Risks of hepatocellular carcinoma (HCC) following hepatitis B and/or hepatitis C virus (HBV/HCV) infection are well known, those for other cancers are less well understood. The aim was to quantify the risk of cancers among persons diagnosed with HBV/HCV infections., Methods: The data from a cohort of 39109 HBV, 75834 HCV, and 2604 HBV/HCV co-infected persons notified to the State health department, 1990-2002, were probabilistically linked to the Cancer Registry and standardised incidence ratios (SIRs) for cancer were calculated., Results: The match rate for any cancer was 2.7%, 2.3% and 3.3% for HBV, HCV and HBV/HCV co-infected notifications. SIRs for HCC were 30.6 (95% CI 25.7-36.5), 22.7 (95% CI 19.1-26.5) and 30.3 (95% CI 13.6-67.5), respectively. Increased risk was detected for Burkitt's lymphoma and HBV (SIR 12.9, 95% CI 5.4-30.9) and immunoproliferative malignancies following HCV (SIR 5.6, 95% CI 1.8-17.5)., Conclusions: The risk of HCC in the infected cohort was 20-30 times greater than in the uninfected population with SIRs two to three times greater than those for the other HBV/HCV infection associated cancers. The modest though significant risk of immunoproliferative malignancies associated with HCV infection is consistent with recent findings.

Objective: The effectiveness of the National Death Index (NDI) in identifying deaths among different populations has been studied before. Prisoners represent a segment of the population that might be expected to be difficult to link. The objective of this research was to evaluate the accuracy of the Australian NDI to ascertain the mortality status of prisoners in New South Wales, Australia., Methods: Data on 311 inmates who had died in custody between January 1988 and March 2003, and on 7,558 inmates known to be alive at the end of May 2003, were matched to the NDI database. Matching was undertaken using a probabilistic linkage method followed by a clerical review. The underlying causes of death reported by the NDI were compared against those reported by the NSW Coroner and held at the Legal Branch of the Department of Corrective Services., Results: Linkage correctly identified 275 of the 311 known deaths (sensitivity: 88.4%). Of the 7,558 prisoners known to be alive in custody at the end of May 2003, linkage to the NDI incorrectly identified 23 as dead (specificity: 99.7%). Cause of death was accurately reported by the NDI for 95.5% of deaths identified by the linkage., Conclusion: The results of this study show that the NDI is an accurate and feasible means for evaluating mortality among prisoners. The nature of the prisoner population makes the linkage a difficult task for the NDI. The success of the data linkage depends on the extent and accuracy of information contained in the index file and type and quality of information available.

Objectives: To assess whether workers at Lucas Heights Science and Technology Centre (LHSTC) have different levels of mortality from the New South Wales (NSW) and Australian populations., Methods: A retrospective cohort study was undertaken at LHSTC. Data on 7,076 workers employed between 1957-98 were abstracted from personnel, dosimetry, and medical files. Deaths registrations in the cohort were identified to 1998 through electronic linkage of records with NSW and national registers of cancer incidence and mortality. Two inception cohorts were defined as including 4,717 and 3,543 workers in employment between 1972-98 and 1980-98, to examine cancer mortality and all-cause mortality respectively., Results: All-cause mortality was 31% lower than the national rates; all-cancer mortality was 19% below the NSW rate. Of 37 specific cancers and groups of cancers examined, statistically significant excesses relative to NSW rates were observed only for pleural cancer mortality (SMR = 21.11; 95% Cl 8.79-50.72)., Conclusions: The observed increase in the risk of cancer of the pleura was probably due to unmeasured exposures, given the lack of an established association with radiation exposure and the strong link to asbestos exposure.