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Biomedical subjects

M G Law

Publications and source records attributed to M G Law.

At least 37 records · Page 2Linked to original sources
PubMed2000

B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS.

OBJECTIVES: To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection. DESIGN AND SETTING: Case-control study in Sydney, Australia. PARTICIPANTS AND METHODS: Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups. RESULTS: In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18). CONCLUSIONS: Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.

Adult↗
PubMed2000

Estimating the population impact in Australia of improved antiretroviral treatment for HIV infection.

OBJECTIVE: To estimate the reduction in AIDS incidence, if any, which has occurred in Australia following the availability of new combination antiretroviral treatments from 1995. DESIGN: Analyses were based on national surveillance data. METHODS: Back-projection analyses based on quarterly AIDS counts to the end of 1994 were used to estimate the numbers of AIDS diagnoses which would have occurred if new treatments had not reduced the rate of progression to AIDS. Estimates of the reduction in AIDS diagnoses between 1995 and 1998 were made by subtracting the observed delay-adjusted AIDS counts from the predicted AIDS incidence. RESULTS: AIDS incidence between 1995 and 1998 was estimated to have been reduced by 1093 cases (33%) following the availability of new antiretroviral treatments (95% confidence interval 831 (25%) to 1425 (43%) cases). The majority of this reduction in AIDS incidence was estimated to have occurred during 1997 (434 cases) and 1998 (427 cases). CONCLUSIONS: AIDS incidence in Australia has declined since 1995 coincidental with introduction of new antiretroviral treatments. In particular, the more rapid decline in AIDS incidence since mid-1996 coincided with the availability and widespread uptake of combinations including protease inhibitors.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997).

The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.

Anti-HIV Agents↗
PubMed1999

Risk of cancer in people with AIDS.

OBJECTIVES: To determine whether the incidence of cancers other than the AIDS-defining cancers is increased in people with AIDS, and to determine if cancer incidence increases with time, a surrogate marker of declining immune function. DESIGN: Register-based retrospective cohort study in New South Wales, Australia. Age-, sex-, and period-adjusted standardized incidence ratios (SIR) were calculated for individual cancers occurring in 1980-1993 in people with AIDS registered before 1996. RESULTS: During the study period, 3616 people were registered with AIDS; 716 cases of AIDS-defining cancer and 62 cases of non-AIDS-defining cancer were identified. People with AIDS had a significantly increased incidence of Hodgkin's disease [SIR 18.3; 95% confidence interval (CI) 8.39-34.8], multiple myeloma (SIR 12.1; 95% CI 2.50-35.4), leukaemia (SIR 5.76; 95% CI 1.57-14.7), lip cancer (SIR 5.94; 95% CI 1.92-13.8) and lung cancer (SIR 3.80; 95% CI 1.39-8.29). The incidence of Hodgkin's disease increased significantly around the time of AIDS diagnosis (P = 0.008 for trend with time), suggesting an association with immunodeficiency. CONCLUSIONS: This study provides strong support for the hypothesis that Hodgkin's disease is an AIDS-associated condition. There was an increased incidence of several other forms of cancer, some of which are known to occur at increased rates in transplant recipients who have received immunosuppressive therapy. Improved survival in people with HIV infection may lead to increases in the number that develop these forms of cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study.

BACKGROUND: Apart from the small number of iatrogenic and familial cases, the cause of most cases of Creutzfeldt-Jakob disease (CJD) is not known. We aimed to identify risk factors for sporadic CJD. METHODS: In a case-control study, we compared the medical history and selected demographic characteristics of 241 definite (neuropathologically confirmed) and probable (clinically likely) patients with CJD, ascertained from the Australian National Creutzfeldt-Jakob Disease Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls, recruited from the community by random telephone interview in August, 1997. Standard logistic regression was used for the comparisons. FINDINGS: Surgical procedures were significantly associated with the development of sporadic CJD. This risk progressively increased with the number of surgical treatments to a maximum for three procedures (odds ratio 2.13 [95% Cl 1.34-3.41], p=0.002). There was also a significant association between risk of CJD and residence or employment on a farm (p<0.001) or market garden (p=0.002) for longer than 10 years. We found no significant risk associated with a history of blood transfusion, organ transplantation, major dental work, or occupation. INTERPRETATION: Our findings accord with the hypothesis that a range of surgical treatments may serve as unrecognised contamination events and account for a proportion of cases of sporadic CJD. Possible biases in different methods and times for the acquisition of data on cases and controls suggest our findings need to be replicated in independent studies with community controls.

Adolescent↗
PubMed1999

AIDS diagnoses at higher CD4 counts in Australia following the introduction of highly active antiretroviral treatment.

OBJECTIVES: To assess whether AIDS cases in Australia have been diagnosed at higher CD4 counts since the widespread availability of highly active antiretroviral treatment (HAART) in mid-1996. METHODS: Data on the CD4 count at AIDS diagnosis for AIDS cases diagnosed between 1 January 1992 and 31 December 1997, and reported to the National AIDS Registry in Australia by 31 March 1998, were analysed. The median CD4 count at AIDS diagnosis, and the proportions of AIDS diagnoses with a CD4 count above 100 cells/microl, and above 200 cells/microl, were calculated by the year of diagnosis, both for all AIDS-defining illnesses, and for each illness separately. Analyses were also stratified by the time interval between HIV and AIDS diagnoses (less than or equal to, or more than, 3 months) because people diagnosed with HIV close to the diagnosis of AIDS would generally not have received any antiretroviral treatment before the diagnosis of AIDS, and so no trends in CD4 counts at the diagnosis of AIDS would be expected in this group. RESULTS: There was an increase in CD4 count at AIDS diagnosis in 1996 and 1997, although this increase was only apparent for AIDS-defining illnesses other than Pneumocystis carinii pneumonia (PCP), and was limited to AIDS cases diagnosed with HIV more than 3 months before AIDS. In cases of AIDS other than PCP, and diagnosed with HIV more than 3 months before AIDS, the median CD4 count increased from 50 cells/microl in 1995 to 80 cells/microl in 1996 and 134 cells/microl in 1997. CONCLUSIONS: There has been an increase in the CD4 count at AIDS diagnosis for most AIDS-defining illnesses in Australia coincident with the widespread availability of HAART.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Urine flow rates and residual urine volumes in urogynecology patients.

Two hundred and fifty consecutive women referred because of symptoms of lower urinary tract dysfunction underwent a full clinical and urodynamic assessment. Their urine flow rates and residual urine volumes were analyzed. The urine flow rates of the urogynecology patients were found to be significantly less than those of an asymptomatic population. There were significant declines in urine flow rates in the presence of a previous hysterectomy and with increasing grades of prolapse, particularly uterine prolapse, cystocele and enterocele. Unlike the normal female population, there was also deterioration with increasing parity and age, the latter largely due to the increasing incidence of hysterectomy and prolapse with age. The 10th centile of the Liverpool Nomogram for the maximum urine flow rate was found to be the most useful discriminant for a final urodynamic diagnosis of voiding difficulties. Most urogynecology patients have no or small residual urine volumes, 74% <10 ml and 81% <30 ml (vs 95% <30 ml in asymptomatic women). In urogynecology patients residuals were larger where there had been a prior hysterectomy or with grade 2 or higher uterine prolapse, cystocele and enterocele. Mean residual was 14.8 ml (vs 4.8 ml in asymptomatic women). These data indicate a higher incidence of voiding difficulties (abnormally slow urine flow (under 10th centile) and/or abnormally high residual urine volume (over 30 ml) in urogynecology patients, particularly those with higher grades of prolapse and with prior hysterectomy.

Female↗
PubMed1999

Modelling the hepatitis C virus epidemic in Australia. Hepatitis C Virus Projections Working Group.

INTRODUCTION: In Australia, to the end of 1997, more than 110,000 people have been diagnosed with hepatitis C virus (HCV) antibodies and reported to State/Territory surveillance systems. The available data indicate that the overwhelming majority (around 80%) of people with HCV antibodies were infected through injecting drug use. METHODS: Models of the HCV epidemic in Australia were developed based on estimates of the pattern of injecting drug use in Australia. Estimates of HCV infections due to injecting drug use thus obtained were then adjusted to allow for HCV infections resulting from other transmission routes. Projections of cirrhosis and hepatocellular carcinoma (HCC) resulting from HCV were obtained by combining modelled HCV incidence with estimates of the progression rates to these outcomes. RESULTS: Based on the models, it was estimated that there were 196,000 (lower and upper limits of 149,000 and 234,000) people in Australia living with HCV antibodies at the end of 1997, with HCV incidence in 1997 estimated to be 11,000 (8500-13,500). It was estimated that 8500 (4000-13,000) people were living with HCV-related cirrhosis in 1997 and that there were 80 (40-125) incident cases of HCV-related HCC. DISCUSSION: Model-based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV-related cirrhosis and the incidence of HCV-related HCC will more than double in Australia by 2010.

Australia↗
PubMed1998

HIV disease progression in Australia in the time of combination antiretroviral therapies.

OBJECTIVE: To examine the effect of recent developments in antiretroviral therapy on HIV disease progression and survival. DESIGN: Retrospective cohort study. PARTICIPANTS AND SETTING: Two cohorts of people with HIV were defined retrospectively from the records of a large immunology laboratory. The first cohort were subjects whose CD4+ T cell counts had dropped to 200 x 10(6)/L during 1990, and the second were subjects whose CD4+ T cell counts had dropped to 200 x 10(6)/L in 1994. MAIN OUTCOME MEASURES: HIV disease progression and survival was determined over a minimum three years of follow-up for each cohort (i.e., 1990-1993; 1994-1997). RESULTS: 346 subjects were included in the analysis (193 subjects from 1990 and 153 from 1994). The relative risk of progression to AIDS in the 1994 cohort compared with the 1990 cohort was 0.57 (95% confidence interval, 0.35-0.91; P = 0.018) and the relative risk of death was 0.20 (95% confidence interval, 0.08-0.49; P < 0.001). CONCLUSIONS: There were 43% fewer AIDS cases and 80% fewer deaths in the time following the increased availability of combination antiretroviral therapy in Australia.

Adult↗
PubMed1998

Time trends in HIV infection among pregnant women in Europe.

OBJECTIVE: To estimate time trends in HIV prevalence among pregnant women delivering livebirths in 14 European countries using a uniform methodology. METHODS: A form of back-projection was used to estimate HIV prevalence among pregnant women based on reported cases of AIDS due to perinatally acquired HIV infection. The method used estimates the rate of progression to AIDS in children with HIV, and the rate of transmission of HIV from mother to child, derived from published studies. RESULTS: The prevalence of HIV among pregnant women delivering livebirths was estimated to be highest in Spain (2.61 per 1000 livebirths in 1992-1993), relatively high (> or = 0.3 per 1000 livebirths) throughout the period 1984-1993 in France, Italy and Switzerland, and low (< 0.2 per 1000 livebirths) in Germany, The Netherlands and Scandinavia. There were large and statistically significant increasing trends in the estimated HIV prevalence among pregnant women in Portugal (an estimated 77% increase per 2-year period), Spain (40% increase) and the United Kingdom (77% increase; all P < 0.001). Statistically significant increasing trends of a smaller magnitude were estimated for France (24% increase) and Italy (23% increase; both P < 0.001). CONCLUSIONS: Sharp increases in HIV prevalence among pregnant women were estimated for several European countries, whereas in other countries no trends in the estimated prevalence were detected.

Adolescent↗
PubMed1998

Rising incidence of oesophageal adenocarcinoma in men in Australia.

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982-1993 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.

Adenocarcinoma↗
PubMed1997

A note on the grouping of surveillance data when adjusting for reporting delays.

Analyses that adjust disease incidence data for reporting delays are often based on grouped data. A way of grouping data based on the quarter in which a case is reported, using all cases reported by a given cutoff date, is compared with the usual method of categorization based on a time-delay between diagnosis and reporting. The two methods of tabulation are illustrated using cases of the acquired immunodeficiency syndrome (AIDS) diagnosed and reported in Australia. A simple simulation study confirms that estimates of adjusted quarterly AIDS counts based on the quarter of report grouping are less variable than those based on the time-delay grouping.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Prognosis of Kaposi's sarcoma as an initial and later AIDS associated illness.

BACKGROUND: The natural history of Kaposi's sarcoma (KS) as a primary presentation of AIDS has been well defined, but little is known about the prognosis of KS following a different AIDS defining illness (ADI). PATIENTS AND METHODS: Retrospective review of 852 consecutive individuals diagnosed with AIDS at Fairfield Hospital between 1984 and 1994. Demographic data, year of diagnosis, CD4 cell counts, treatment for KS and PCP prophylaxis were included in the analysis. Survival following a diagnosis of KS was evaluated, adjusting for the effects of year of diagnosis, primary or secondary KS and degree of immunodeficiency. RESULTS: The overall cumulative incidence of KS by three years post ADI was 34%. Median survival for KS as an ADI (n = 130) was 20 months versus 9 months for KS subsequent to another ADI (n = 75, P < 0.001). Those with KS as an ADI had a higher CD4 count (median 90 vs. 11, P < 0.001), lower incidence of visceral disease (5 of 130 vs. 11 of 75, P = 0.032) and fewer associated AIDS related illnesses (1 vs. 2, P < 0.001). Poorer survival following diagnosis of KS was associated with a lower CD4 count at diagnosis of KS (P = 0.002), extensive cutaneous or visceral KS at diagnosis (P = 0.009 and P < 0.001 respectively) and with the number of associated AIDS related illnesses (P < 0.001). A multivariate analysis suggested that, after adjusting for these factors, there was no difference in survival between primary and secondary KS. CONCLUSION: We found no difference in survival between primary and secondary KS after adjusting for potential confounding factors. We cannot exclude, however, that the greater incidence of visceral disease identified in secondary KS reflects an inherently more aggressive biology.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage.

The relationship between the presence and severity of AIDS dementia complex (ADC) and the levels of human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF) were assessed. Nineteen patients with ADC (stages 1-3), 6 without ADC (group 1), and 10 (group 2) without ADC but with cryptococcal meningitis or progressive multifocal leukoencephalopathy were studied. There was a significant relationship between increasing CSF virus burden and ADC severity (P = .0006) but not with plasma burden and ADC severity. In group 2, CSF HIV-1 RNA levels in patients with cryptococcal meningitis were elevated. These results show that CSF HIV-1 RNA concentrations correlate well with ADC severity but may also be increased by central nervous system infections, such as cryptococcal meningitis.

AIDS Dementia Complex↗