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Biomedical subjects

J M Kaldor

Publications and source records attributed to J M Kaldor.

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

Incidence and risk factors for urethral and anal gonorrhoea and chlamydia in a cohort of HIV-negative homosexual men: the Health in Men Study.

BACKGROUND: Early detection and treatment of bacterial sexually transmitted infections has been advocated as an HIV prevention strategy. AIM: To inform screening guidelines, the incidence and risk factors for urethral and anal gonorrhoea and chlamydia were studied in a prospective cohort of community-based HIV negative homosexual men in Sydney, New South Wales, Australia. METHODS: All participants were offered annual screening for gonorrhoea and chlamydia (study-visit diagnoses) on urine and anal swabs using nucleic acid amplification. Participants also reported diagnoses of gonorrhoea and chlamydia made elsewhere between interviews (interval diagnoses). All diagnoses were summed to create a combined incidence rate, and detailed data on specific sexual practices with casual and regular partners were collected. RESULTS: Among 1427 men enrolled, the combined incidence rates were 3.49 and 2.96 per 100 person-years for urethral and anal gonorrhoea, respectively; and 7.43 and 4.98 per 100 person-years for urethral and anal chlamydia, respectively. Urethral infections were associated with unprotected anal intercourse (UAI) with HIV-positive partners (hazard ratio (HR) = 2.58, 95% CI 1.10 to 6.05 for urethral gonorrhoea) and with frequent insertive oral sex (p for trend 0.007 for urethral chlamydia). Anal infections were associated with receptive UAI (p for trend 0.001 for both anal gonorrhoea and chlamydia) and other receptive anal sexual practices. Stratified analyses showed the independence of the associations of insertive oral sex with urethral infections and of non-intercourse receptive anal practices with anal infections. CONCLUSION: Incident gonorrhoea and chlamydia were common. Risk behaviours for both urethral and anal infections were not restricted to UAI. Screening that includes tests for anal and urethral infections should be considered for all sexually active homosexual men, not just for those who report UAI.

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

Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies.

A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4-67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22-0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.

Adult↗
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

Heterozygosity for CCR5-Delta32 but not CCR2b-64I protects against certain intracellular pathogens.

OBJECTIVE: To determine the association between CCR5 and CCR2b genotype and the clinical manifestation of first and subsequent AIDS-defining illnesses (ADIs). METHODS: The distribution of ADIs was examined by CCR5 and CCR2b genotype in a subset of homosexual men enrolled in the Sydney AIDS Prospective Study. The expected number of ADIs was calculated from rates observed in the same tertiary hospital over the same period. RESULTS: Information on initial ADI was collected for 117 homosexual men diagnosed with AIDS before January 1998. Of these individuals, 17 were heterozygous for the CCR5-Delta32 mutation and 11 were heterozygous for CCR2b-64I. The number of observed cases of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) and cryptosporidiosis reported as a first ADI was substantially fewer in people heterozygous for the CCR5-Delta32 mutation than for those without the mutation, despite similar age, CD4 T-cell count at AIDS diagnosis, year of AIDS diagnosis and receipt of antiretroviral treatment. In addition, among individuals heterozygous for CCR5-Delta32 there were fewer cases of PCP, toxoplasmosis, MAC, and cryptosporidiosis observed as subsequent ADIs compared to the number expected, based on rates measured in the same hospital during the same period (seven observed vs. 24 expected, RR = 0.3, 95% CI = 0.01-0.6). The distribution of first and subsequent ADIs did not differ from the number expected in individuals heterozygous for the CCR2b-64I mutation. CONCLUSION: Results from this study show that heterozygosity for CCR5-Delta32 but not CCR2b-64I appears to protect against opportunistic infections.

AIDS-Related Opportunistic Infections↗
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

Use of interventions for reducing mother-to-child transmission of HIV in Australia.

OBJECTIVE: To describe the extent and outcome of use of interventions for reducing the risk of HIV transmission from mother to child in Australia. DESIGN: National surveillance for perinatal exposure to HIV. PARTICIPANTS AND SETTING: Notified cases of HIV infection in women in Australia and their perinatally exposed children, 1982-1999. OUTCOME MEASURES: Trends over time in use of interventions (antiretroviral therapy in pregnancy, elective caesarean delivery and avoidance of breastfeeding) and perinatally acquired HIV infection. RESULTS: By 31 March 2000, 204 children were reported as having been born in 1982-1999 to 162 women whose HIV infection had been diagnosed by 31 December 1999. The child's HIV infection status was established for 182 (89.2%); the mother's HIV infection was diagnosed antenatally in 91 of these cases (50%). Among women diagnosed antenatally, use of elective caesarean delivery and antiretroviral therapy in pregnancy increased significantly, from 3% and 14% by women whose children were born in 1982-1993, to 21% (P=0.01) and 88% (P<0.001), respectively, by women whose children were born in 1994-1999. Most women (95%) diagnosed antenatally avoided breastfeeding their children. The percentage of infected children born to women diagnosed antenatally declined from 26% among children born in 1982-1993 to 19% among those born in 1994-1999. The percentage of infected children was significantly lower among those whose mothers used antiretroviral therapy in pregnancy (11% versus 36%; P=0.03). CONCLUSION: Antiretroviral use in pregnancy, elective caesarean delivery and avoidance of breastfeeding have been effective interventions for reducing the risk of mother-to-child HIV transmission in Australia. While the rate of perinatal HIV transmission has declined, it remains high in comparison with rates reported from other industrialised countries.

Acquired Immunodeficiency Syndrome↗
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

Spectrum of AIDS-defining illnesses in Australia, 1992 to 1998: influence of country/region of birth.

OBJECTIVE: To examine the influence of country/region of birth on spectrum of AIDS-defining illness. METHODS: National surveillance data for 4,629 adolescents and adults diagnosed with AIDS from 1992 through 1998 were analyzed. Country of birth was grouped into five broad categories (Australia, other predominantly industrialized country regions, sub-Saharan Africa, Asia-Pacific, and other regions with predominantly developing countries). Proportions of AIDS-defining illnesses were calculated and compared by country/region of birth. Role of country/region of birth in the distribution of AIDS-defining illnesses was further assessed using logistic models. RESULTS: Of the 4,488 (97.0%) AIDS cases with country of birth recorded, 1,120 (25.0%) were born outside Australia. In multivariate analyzes, AIDS cases born in sub-Saharan Africa had an increased risk of tuberculosis (odds ratio [OR], 18.7; confidence interval [CI], 9.2-38.2) and cryptococcosis (OR, 2.4; CI, 1.1-5.4), but a decreased risk of esophageal candidiasis (OR, 0.3; 0.1-0.8) and Pneumocystis carinii pneumonia (OR, 0.5; 0.3-0.9) compared with AIDS cases born in Australia. Tuberculosis risk was also elevated among AIDS cases born in Asia-Pacific (OR, 9.6; 5.3-17.5) and other developing country regions (OR, 3.1; 0.9-10.4). Risk of AIDS-defining illnesses was similar for AIDS patients born in Australia and other industrialized country regions. Country of birth had no influence on risk of cytomegalovirus (CMV)-related disease and Mycobacterium avium complex (MAC) infection. Differential AIDS-defining illness risk was more pronounced among AIDS patients born in developing countries who had resided in Australia for less time. CONCLUSIONS: Differential risk by country/region of birth for some AIDS-defining illnesses, especially among more recent arrivals from developing countries, suggests that environmental microbial habitats are important determinants of opportunistic infection risk. Similar risk of CMV disease and MAC infection is consistent with the ubiquitous nature of these microbial agents and suggests that previously reported low prevalence from developing countries may reflect poor diagnostic capacity rather than level of risk.

AIDS-Related Opportunistic Infections↗
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↗