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Biomedical subjects

M G Law

Publications and source records attributed to M G Law.

At least 19 recordsLinked to original sources
PubMed2006

Extreme cause-specific mortality in a cohort of adult prisoners--1988 to 2002: a data-linkage study.

OBJECTIVES: Describe the standardized mortality ratio (SMR) and its trend in adults who have served time in prison. DESIGN: A retrospective cohort study of 85,203 adults imprisoned in New South Wales (NSW), Australia, between 1 January 1988 and 31 December 2002. METHODS: We obtained information on deaths by record linkage with the Australian National Death Index (NDI). Mortality rates were estimated using the person-time method. SMRs were calculated using sex, age, and calendar-specific death rates from the NSW population. Time trends in SMRs were assessed using the test for linear trends. RESULTS: The median overall follow-up of the cohort was 7.7 years. We identified 5137 deaths (4714 men, 423 women) among the cohort of which the vast majority (4834, 94%) occurred following release from custody. All-cause SMR was 3.7 (95% CI: 3.6-3.8) in men and 7.8 (95% CI: 7.1-8.5) in women. SMRs were substantially raised for deaths due to mental and behavioural disorders (men: 13.2, 95% CI: 12.3-14.0; women: 62.8, 95% CI: 52.7-74.9) and drug-related deaths (men: 12.8, 95% CI: 12.2-13.5; women: 50.3, 95% CI: 43.7-57.8). The SMR for death by homicide was 10.2 (95% CI: 8.9-11.7) in men and 26.3 (95% CI: 17.8-39.0) in women. Aboriginal men were 4.8 times, and Aboriginal women 12.6 times, more likely to die than the general NSW population. Over the study period on average all-cause SMR decreased significantly in men (p = 0.003) and women (p = 0.05) largely due to the decline in SMRs for drug-related deaths and suicide. CONCLUSION: In the largest study so far reported, mortality of male and female offenders was far greater than expected for all major causes, especially deaths caused by drug overdose. Despite some indication of a reduction in excess mortality in recent years, there remains an overwhelming need for enhanced responses to mental health and drug problems for people who have been in prison.

Adult↗
PubMed2006

Potential biases in estimates of hepatitis C RNA clearance in newly acquired hepatitis C infection among a cohort of injecting drug users.

Estimates of hepatitis C virus (HCV) clearance following acute infection range from 14 to 46%. This wide range is likely to be due to the characteristics of the populations studied and analysis methods. This paper examines how differing definitions of clearance parameters affect estimates of viral clearance in a cohort of 85 injecting drug users with newly acquired HCV infection. Kaplan-Meier estimates of time to HCV clearance were determined using varying definitions of eligible cohort, viral clearance, date of infection and date of clearance. Based on which combinations of definitions were used, the number of subjects eligible for analysis ranged from 27 to 75, clearance rate ranged from 14 to 68% and time to achieving 25% clearance ranged from approximately 5 months to 14 months. Standardized definitions and methodologies are required to enable valid comparisons of rates of clearance across newly acquired HCV infection natural history studies.

Bias↗
PubMed2006

The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study.

BACKGROUND: The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) Study, a prospective observational study on a cohort of 23 468 patients with HIV infection, indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). However, it remains unclear whether the observed increase in the rate of MI in this population can be attributed to changes in conventional cardiovascular risk factors. OBJECTIVE: To compare the number of MIs observed among participants in the D:A:D Study with the number predicted by assuming that conventional cardiovascular risk equations apply to patients with HIV infection. METHODS: The Framingham equation, a conventional cardiovascular risk algorithm, was applied to individual patient data in the D:A:D Study to predict rates of MI by duration of CART. A series of sensitivity analyses were performed to assess the effect of model and data assumptions. Predictions were extrapolated to provide 10-year risk estimates, and various scenarios were modelled to assess the expected effect of different interventions. RESULTS: In patients receiving CART, the observed numbers of MIs during D:A:D follow up were similar to or somewhat higher than predicted numbers: 9 observed vs 5.5 events predicted, 14 vs 9.8, 22 vs 14.9, 31 vs 23.2 and 47 vs 37.0 for<1 year, 1-2 years, 2-3 years, 3-4 years and >4 years CART exposure, respectively. In patients who had not received CART, the observed number of MIs was fewer than predicted (3 observed vs 7.6 predicted). Nine per cent of the study population have a predicted 10-year risk of MI above 10%, a level usually associated with initiation of intervention on risk factors. CONCLUSIONS: A consistent feature of all analyses was that observed and predicted rates of MI increased in a parallel fashion with increased CART duration, suggesting that the observed increase in risk of MI may at least in part be explained by CART-induced changes in conventional risk factors. These findings provide guidance in terms of choosing lifestyle or therapeutic interventions to decrease those risk factors in much the same way as in persons without HIV infection.

Adult↗
PubMed2005

Randomized, placebo-controlled, phase I/IIa evaluation of the safety and immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in HIV-1 infected subjects.

We conducted a randomized, placebo-controlled double-blind trial to examine the safety and immunogenicity of a candidate HIV therapeutic vaccine based upon a recombinant fowl pox virus capable of coexpressing the human cytokine interferon-gamma and/or genes from HIV-1. Thirty-five eligible subjects were randomized (12 placebo, 11 fowlpox + HIV genes, 12 fowl pox + HIV genes + interferon gamma). All but one subject (placebo group) received three immunizations (by intramuscular injection on day 0, week 4 and week 12) and all completed 52 weeks of follow-up. All subjects continued to take combination antiretroviral therapy for the duration of study. There were no significant toxicity or safety concerns and the distribution of adverse events and their severity was consistent across each randomly assigned vaccine group. Comparison of placebo recipients with the combined recipients of the two vaccine constructs, in terms of anti-HIV gag ELISpot or lymphoproliferative responses, tended to favour the placebo group, but were not significantly different (difference in time-weighted mean change from baseline = 56 Spot forming units (sfu)/10(6) PBMC; p = 0.062 and 4.4 SI; p = 0.337). There were no significant changes in CTL responses by standard Cr(51) release assay. Anti-FPV antibodies were detected by week 14 in 0 placebo and 20 (87%) vaccine recipients. Although safe, neither vaccine construct appeared to possess detectable T-cell mediated anti-HIV immunogenic properties in HIV infected individuals, as measured by standard T cell assays.

AIDS Vaccines↗
PubMed2004

Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, Australia.

OBJECTIVES: To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. METHODS: All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985-2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985-1991), dual therapy (1992-1995) or HAART (1996-2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. RESULTS: Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/microL in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985-1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. CONCLUSIONS: Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis.

Adolescent↗
PubMed2003

Predicting progression to cirrhosis in chronic hepatitis C virus infection.

A systematic evaluation of published studies was undertaken to identify factors associated with accelerated fibrosis progression in patients with chronic hepatitis C virus (HCV) infection. An ecologic analysis was used to estimate relative risk (RR) of cirrhosis across four study methodologies: liver clinic series, post-transfusion cohorts, community-based studies and blood donor series. In each study category, the following factors were independently associated with disease progression: male sex (RR = 1.08); heavy alcohol consumption (RR = 1.61); elevated serum ALT levels (RR = 1.23) and histology demonstrating high-grade necro-inflammatory activity. After adjusting for these cofactors, older age at HCV infection and acquisition of HCV through blood transfusion were not implicated in influencing disease outcome. Although not able to be examined in this study,co-infection with HIV, and to a lesser extent HBV, is also likely to result in worse outcomes for patients with chronic HCV infection. Virological factors such as HCV genotype, viral load and quasispecies diversity are less likely to be important. A Weibull distribution was used to model disease progression at a population level. The influence of cofactors on individual prognosis was examined and an algorithm to predict the risk of subsequently developing cirrhosis is presented.

Adult↗
PubMed2002

Predictors of recent HIV testing in homosexual men in Australia.

OBJECTIVES: To describe time trends and other predictors of recent HIV testing among homosexual men enrolled in behavioural surveillance studies in Australia. METHODS: Repeated cross-sectional studies during the period 1996-2001 in Australian capital cities. Men were recruited from a variety of community-based settings, including gay community outdoor events, sex on premises venues, and social venues. They underwent a brief self-administered questionnaire in which they reported their HIV status, HIV-testing history, sexual behaviour and demographic information. RESULTS: Questionnaires were returned for 22,161 HIV-negative or status-unknown participants. While 85.3% had ever tested for HIV, 57.6% had tested in the last 12 months. Recent testing was greater in those living in Sydney, in younger men, in gay-identified men, in gay community-attached men, in those who reported unprotected anal intercourse and a higher number of sexual partners, and in partners of HIV-positive men. Although recent testing declined from 1996 to 2001, this trend was no longer significant when adjusted for other testing predictors. CONCLUSIONS: In Australia, HIV testing among gay men decreased slightly from 1996 to 2001, but the trend was not significant when adjusted for other predictors. Testing levels were highest among those at highest risk of HIV infection, and lowest among non gay-identified and non gay-community attached homosexual men.

Adult↗
PubMed2001

Modelling the effect of combination antiretroviral treatments on HIV incidence.

OBJECTIVE: To assess the competing effects on HIV incidence in homosexual men of the decreased infectiousness of men with HIV receiving effective combination antiretroviral treatments and homosexual men engaging in unprotected anal intercourse with increased numbers of partners (levels of unsafe sex). METHODS: A mathematical model of HIV transmission in homosexual men was developed, based on the HIV epidemic in Australia in 1996, when effective antiretroviral treatments first became widely available. Uncertainties in parameters were modelled using 1000 simulations. The effect of treatments on decreasing infectiousness was randomly sampled with a median 10-fold decrease in infectiousness (range 100-fold to no decrease). Levels of unsafe sex were randomly sampled with a median 50% increase in unsafe sex (range 100% to no increase). The percentage change in HIV incidence after one year was obtained by comparison with a null model in which there was no decrease in infectiousness as a result of treatment and no change in unsafe sex. RESULTS: Results of the models suggested that whereas increased levels of unsafe sex were linearly associated with increases in HIV incidence, decreases in infectiousness because of treatments were non-linearly associated with decreases in HIV incidence. An assessment of the competing effects suggested that decreases in infectiousness of two-, five-, and 10-fold would be counterbalanced by increases in unsafe sex of approximately 40, 60 and 70%, respectively. CONCLUSION: These models suggest that apparently large decreases in infectiousness as a result of treatment could be counterbalanced in terms of new HIV infections by much more modest increases in unsafe sex.

Anti-HIV Agents↗
PubMed2001

Decreasing rates of Kaposi's sarcoma and non-Hodgkin's lymphoma in the era of potent combination anti-retroviral therapy.

OBJECTIVE: To describe the changing incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) in people with HIV in Australia during the time period of introduction of potent combination anti-retroviral therapy. DESIGN: A national, population-based linkage study of cancer and HIV registration data. METHODS: We calculated person-year rates of KS and NHL in people after reporting of HIV diagnosis. Trends in cancer incidence rates were examined, based on four time periods defined by the availability of specific anti-retroviral therapies. RESULTS: Linkage identified 206 cases of KS and 235 cases of NHL in 8108 people reported with HIV infection. There was an increasing trend in NHL incidence rates over the four time periods (P for trend, 0.012), but incidence for the period since the availability of the new therapies was significantly lower than that for the period immediately prior (incidence rate ratio 0.58; 95% confidence interval, 0.36-0.92). Incidence of KS had been decreasing prior to the new therapies and declined further since their widespread use (P for trend, 0.045). CONCLUSIONS: Population-based incidence rates of AIDS related KS and NHL have decreased since the widespread use of potent anti-retroviral therapies in Australia. NHL incidence decreased less than KS, and NHL is now the most common AIDS-associated cancer in Australia.

AIDS-Related Opportunistic Infections↗
PubMed2001

The cost of hepatitis C and the cost-effectiveness of its prevention.

Hepatitis C infection is an emerging problem in public health and is now the most common blood-borne infection. The virus imposes a significant personal and social burden on those infected, as well as substantial costs to the health care system. In this paper we report an estimate of the costs of hepatitis C and consider the role such information might play in determining an appropriate preventive strategy. Preventing a single case of HCV would release resources valued Aus $6000 and Aus $19,000, depending on whether production loses were included. This information can be used to derive cost-effectiveness thresholds for any preventive activity, but is not in itself necessary in determining health priorities. Information on the marginal cost-effectiveness of preventive methods is both necessary and sufficient.

Australia↗
PubMed2001

Back-projection estimates of the number of dependent heroin users in Australia.

AIMS: To plan an appropriate response to heroin use in Australia, good estimates are needed of the numbers of dependent heroin users, the group who are most in need of treatment, most at risk of fatal opioid overdose and most at risk of contracting and transmitting blood-borne viruses. METHODS: Back-projection methods were used to estimate the numbers of people starting dependent heroin injecting in Australia between 1960 and 1997. Separate analyses were based on national opioid overdose deaths and numbers of new entrants to methadone treatment in New South Wales (NSW). Estimates of the rates at which dependent heroin users cease heroin use, commence methadone treatment or die from opioid overdoses were estimated from external data sources. RESULTS: Back-projection estimates derived from opioid overdose deaths indicated that there were 104 000 (lower limit of 72 000 and upper limit of 157 000) people who were heroin dependent in Australia between 1960 and 1997. Of these it was estimated that 67 000 (39 000-120 000) were still heroin dependent at the end of 1997. Back-projection estimates based on numbers of new entrants to methadone treatment in NSW indicated that there were 108 000 (82 000-141 000) heroin-dependent people in Australia between 1960 and 1997, of whom 71 000 (47 000-109 000) were estimated to be heroin dependent at the end of 1997. Both analyses indicated that the number of heroin-dependent people in Australia has increased substantially from the early 1970s onwards. CONCLUSIONS: Back-projection estimates based on analyses of treatment entries and opioid overdose deaths provide an additional method for estimating the numbers of heroin-dependent people in the population. The addition of these methods to existing methods, using different data sources and statistical methods, should improve consensus estimates of the numbers of heroin-dependent people.

Adolescent↗
PubMed2001

Variant Creutzfeldt-Jakob disease in Australian blood donors: estimation of risk and the impact of deferral strategies.

BACKGROUND AND OBJECTIVES: In Australia, a policy of deferring donors who have lived in the UK for longer than 6 months between 1980 and 1996 has been instituted to reduce the theoretical risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) through the blood supply. The objective of this report was to refine estimates of the possible risks and benefits of donor-deferral strategies that are aimed at avoiding transmission of vCJD. MATERIALS AND METHODS: Estimates of the effect of donor deferral on the blood supply in Australia were based on a 1998 survey of blood donors. The number of donations from donors potentially infected with vCJD and excluded by donor deferral was estimated based on published estimates of the size of the vCJD epidemic in the UK and assuming that the risk of vCJD in Australian blood donors was proportional to the time lived in the UK between 1980 and 1996. The possible increased number of blood donations that were infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) and made during a window period (as a result of increased donations from first-time donors) was estimated using published methods. RESULTS: A strategy of deferring donations in Australia from people who have lived in the UK for 6 months or longer, between 1980 and 1996, was estimated to result in exclusion of 5.3% of all blood donations, corresponding to 50 100 donations in 1998. It was estimated that the annual number of blood donations made by donors potentially infected with vCJD is 1.15 (range 0.02--31.1, based on the uncertainty in the UK prevalence estimate). Donor deferral was estimated to remove 0.92 (range 0.02--25.1) of these donations. Replacement of 33%, 50% and 100% of excluded donations by donations from first-time donors, was estimated to result in an increase of 0.0010, 0.0019 and 0.0044, respectively, of HIV-infected donations per year donated during the window period; in an increase of 0.021, 0.038 and 0.089, respectively, of HCV-infected donations per year; and in an increase of 0.18, 0.33 and 0.76, respectively, of HBV-infected donations per year. CONCLUSIONS: The large uncertainties involved in these analyses mean that estimates must be interpreted cautiously, but the data does suggest that donor deferral may exclude more donations from donors potentially infected with vCJD than the corresponding increase, caused by donor replacement, of window-period donations possibly infected with HIV, HCV or HBV.

Australia↗
PubMed2001

Estimating progression to cirrhosis in chronic hepatitis C virus infection.

To gain a clearer understanding of the rate of progression to cirrhosis and its determinants in chronic hepatitis C virus (HCV) infection, a systematic review of published epidemiologic studies that incorporated assessment for cirrhosis has been undertaken. Inclusion criteria were more than 20 cases of chronic HCV infection, and information on either age of subjects or duration of infection. Of 145 studies examined, 57 fulfilled the inclusion criteria. Least-squares linear regression was employed to estimate rates of progression to cirrhosis, and to examine for factors associated with more rapid disease progression in 4 broad study categories: 1) liver clinic series (number of studies = 33); 2) posttransfusion cohorts (n = 5); 3) blood donor series (n = 10); and 4) community-based cohorts (n = 9). Estimates of progression to cirrhosis after 20 years of chronic HCV infection were 22% (95% CI, 18%-26%) for liver clinic series, 24% (11%-37%) for posttransfusion cohorts, 4% (1%-7%) for blood donor series, and 7% (4%-10%) for community-based cohorts. Factors that were associated with more rapid disease progression included older age at HCV infection, male gender, and heavy alcohol intake. Even after accounting for these factors, progression estimates were much higher for cross-sectional liver clinic series. Selection biases probably explain the higher estimates of disease progression in this group of studies. Community-based cohort studies are likely to provide a more representative basis for estimating disease progression at a population level. These suggest that for persons who acquire HCV infection in young adulthood, less than 10% are estimated to develop cirrhosis within 20 years.

Adult↗
PubMed2000

How many dependent heroin users are there in Australia?

OBJECTIVE: To estimate the prevalence of dependent or daily heroin users in Australia, and to compare the prevalence in Australia with that in other developed countries. DESIGN: We applied three different methods of estimation (back-projection, capture-recapture, and multiplier) to data on national opioid overdose deaths in Australia, first-time entrants to methadone maintenance treatment, and heroin-related arrests in New South Wales. We compared our estimates with estimates derived by similar methods in countries of the European Union. DATA SOURCES: Data on national opioid overdose deaths were obtained from the Australian Bureau of Statistics. Data on methadone entrants in NSW were extracted from a database maintained by the NSW Department of Health. Data on arrests for heroin-related offences were supplied by the NSW Police Service. RESULTS: The best estimates of the number of dependent heroin users in Australia in 1997-1998 from the three methods of estimation were between 67 000 and 92 000 and the median estimate was 74 000. The population prevalence was 6.9 per 1000 adults aged 15-54 years. The prevalence of heroin dependence in Australia is the same as that in Britain (7 per 1000) and within the range of recently derived estimates in the European Union (3-8 per 1000 adults aged 15-54 years). CONCLUSIONS: Although the exact figures need to be interpreted with caution, our estimates suggest that Australia has a substantial public health problem with dependent heroin use that is of a magnitude similar to that in comparable European societies.

Adolescent↗
PubMed2000

Primary hepatocellular carcinoma in Australia, 1978-1997: increasing incidence and mortality.

OBJECTIVES: To describe trends in primary hepatocellular carcinoma (HCC) incidence and mortality in Australia between 1978 and 1997, and to delineate the effects of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection by examining cases of HCC in Australian-born and overseas-born people separately. DESIGN AND SETTING: Retrospective analysis of national incidence and mortality data in which the underlying cause was coded as HCC (International classification of diseases, ninth revision [ICD-9] code 155.0). MAIN OUTCOME MEASURES: Changes in age-standardised HCC incidence rates in men and women between 1983 and 1996; age-standardised HCC death rates in Australian-born and overseas-born men and women between 1978 and 1997. RESULTS: Age-standardised incidence rates increased in men and women (from 2.06 and 0.57 per 100,000 respectively in 1983-1985 to 3.97 and 0.99 respectively in 1995-1996). Age-standardised death rates increased in Australian-born and overseas-born men and overseas-born women (from 1.43, 2.35 and 0.62 respectively per 100,000 in 1978-1982 to 2.50, 4.41 and 1.36 respectively in 1993-1997). However, death rates in Australian-born women did not increase (0.58 per 100,000 in 1978-1982 and 0.63 in 1993-1997). CONCLUSIONS: HCC incidence and death rates in Australia have increased over the past two decades, except in Australian-born women. A likely explanation for at least a portion of this increase is increased prevalences of HBV and HCV infection in Australia.

Age Factors↗
PubMed2000

A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3.

A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ¿MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.

Adult↗