Rock fracture mean trace length estimation and confidence interval calculation using maximum likelihood methods

There has been a resurgence of interest in the mean trace length estimator of Pahl for window sampling of traces. The estimator has been dealt with by Mauldon and Zhang and Einstein in recent publications. The estimator is a very useful one in that it is non-parametric. However, despite some discussion regarding the statistical distribution of the estimator, none of the recent works or the original work by Pahl provide a rigorous basis for the determination a confidence interval for the estimator or a confidence region for the estimator and the corresponding estimator of trace spatial intensity in the sampling window. This paper shows, by consideration of a simplified version of the problem but without loss of generality, that the estimator is in fact the maximum likelihood estimator (MLE) and that it can be considered essentially unbiased. As the MLE, it possesses the least variance of all estimators and confidence intervals or regions should therefore be available through application of classical ML theory. It is shown that valid confidence intervals can in fact be determined. The results of the work and the calculations of the confidence intervals are illustrated by example. (C) 2003 Elsevier Science Ltd. All rights reserved.

Interval breast cancers in an Australian mammographic screening program

Objective: To determine the incidence of interval cancers which occurred in the first 12 months after mammographic screening at a mammographic screening service. Design: Retrospective analysis of data obtained by crossmatching the screening Service and the New South Wales Central Cancer Registry databases. Setting: The Central & Eastern Sydney Service of BreastScreen NSW. Participants: Women aged 40-69 years at first screen, who attended for their first or second screen between 1 March 1988 and 31 December 1992. Main outcome measures: Interval-cancer rates per 10 000 screens and as a proportion of the underlying incidence of breast cancer (as estimated by the underlying rate in the total NSW population). Results: The 12-month interval-cancer incidence per 10 000 screens was 4.17 for the 40-49 years age group (95% confidence interval [CI], 1.35-9.73) and 4.64 for the 50-69 years age group (95% CI, 2.47-7.94). Proportional incidence rates were 30.1% for the 40-49 years age group (95% CI, 9.8-70.3) and 22% for the 50-69 years age group (95% CI, 11.7-37.7). There was no significant difference between the proportional incidence rate for the 50-69 years age group for the Central & Eastern Sydney Service and those of major successful overseas screening trials. Conclusion: Screening quality was acceptable and should result in a significant mortality reduction in the screened population. Given the small number of cancers involved, comparison of interval-cancer statistics of mammographic screening programs with trials requires age-specific or age-adjusted data, and consideration of confidence intervals of both program and trial data.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

Effect of metabolic inhibitors on cyclosporine pharmacokinetics using a population approach

Drugs known to inhibit the metabolism of cyclosporine are administered concomitantly to those who undergo cardiothoracic transplantation. The aim of this study was to examine in quantitative terms the relationship between cyclosporine oral dose rate and the trough concentration (Css(trough)) at steady state in patients who undergo cardiothoracic transplantation and are administered cyclosporine alone or in combination with drugs known to inhibit its metabolism. Dose and whole blood cyclosporine Css(tough) observations measured using the enzyme-multiplied immunoassay technique (EMIT) (396 observations) or the TDx assay (435 observations) were collected as part of routine blood concentration monitoring from 182 patients who underwent cardiothoracic transplantation. Data were analyzed using a linear mixed-effects modeling approach to examine the effect of metabolic inhibitors on dose-rate-Css(trough) ratio. The mean (and 95% confidence interval) dose-rate-Css(trough) ratio for cyclosporine generated from concentrations measured using EMIT was 94 (82.5-105.5) Lh(-1) for patients administered cyclosporine alone, 66.7 (58.1-75.3) Lh(-1) for patients administered concomitant diltiazem, 47.9 (15.4 -80.4) Lh(-1) for patients administered concomitant itraconazole, 21.7 (14.8-28.5) Lh(-1) for patients administered concomitant ketoconazole, and 14.9 (11.8-18.1) Lh(-1) for patients concomitantly administered diltiazem and ketoconazole. For patients administered concomitant cyclosporine, ketoconazole, and diltiazem, the dosage of cyclosporine, if it is administered alone, should be 20% to achieve the same blood concentrations. This will allow safer drug concentration targeting of cyclosporine after cardiothoracic transplantation.

The epidemiology of Parkinson's disease in an Australian population

A prevalence study of Parkinson's disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53-775). We performed a separate case-control study involving 224 patients with FD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family history. This demonstrates the need for improved understanding of the genetic nature of the disease.

Coronary events and exposure to environmental tobacco smoke: a case-control study from Australia and New Zealand

Objectives-To estimate the relative risk of coronary heart disease (CHD) associated with exposure to environmental tobacco smoke (ETS). Design-Population-based case-control study. Subjects-Cases were 953 people identified in a population register of coronary events, and controls were 3189 participants in independent community-based risk factor prevalence surveys from the same study populations. Setting-Newcastle, Australia and Auckland, New Zealand. Main outcome measures-Acute myocardial infarction or coronary death. Results-After adjusting for the effects of age, education, history of heart disease, and body mass index, women had a statistically significant increased risk of a coronary event associated with exposure to ETS (relative risk (RR) = 1.99; 95% confidence interval (CI)= 1.40-2.81). There was little statistical evidence of increased risk found in men (RR = 1.02, 95% CI = 0.81-1.28). Conclusion-Our study found evidence for the adverse effects of exposure to ETS on risk of coronary heart disease among women, especially at home. For men the issue is unclear according to the data from our study. Additional studies with detailed information on possible confounders and adequate statistical power are needed. Most importantly, they should use methods for measuring exposure to ETS that are sufficiently accurate to permit the investigation of dose-response relationships.

Australian doctors' beliefs and practice regarding Helicobacter pylori

Objective: To determine beliefs and behaviours of Australian doctors regarding Helicobacter pylori. Design: Anonymous reply-paid postal survey mailed in December 1995 and again in March 1996. Subjects: All members on the mailing lists of the Gastroenterological Society of Australia Endoscopy Section (n = 397) and the Australian Society of Infectious Diseases (n = 264; those without medical qualifications were asked not to reply), and 400 general practitioners (GPs) randomly selected from the Royal Australian College of General Practitioners. Main outcome measures: Differences between specialist groups in belief in a causative association between H. pylori and peptic disease and in use of eradication therapy and pre- and post-treatment testing for H. pylori. Results: 92.6% of doctors believed H. pylori causes duodenal ulcer, with GPs significantly less likely to believe than gastroenterologists (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.00-0.81). In duodenal ulcer, 93.4% of doctors believed H. pylori eradication therapy should be given, but fewer (83.4%) claimed to give it always or mostly, with GPs less likely to report giving it than gastroenterologists (OR, 0.06; 95% CI, 0.02-0.19). For non-ulcer dyspepsia, gastrointestinal surgeons were more likely than gastroenterologists to believe in a causative link with H. pylori (OR, 5.6; 95% CI, 3.0-10.7) and in a need for eradication therapy (OR, 3.6; 95% CI, 1.7-7.7). Most doctors (79.3%) believed in confirming the presence of H. pylori before eradication therapy in duodenal ulcer. Only 51.6% believed post-eradication testing necessary (45.5%), yet 79.1% reported performing it. Conclusions: Significant differences exist between specialist groups in beliefs and self-reported behaviours regarding H. pylori.

Opioid overdose mortality in Australia, 1964-1997: birth-cohort trends

Objective: To examine trends in rates of opioid overdose deaths from 1964 to 1997 in different birth cohorts. Design: Age-period-cohort analysis of national data from the Australian Bureau of Statistics. Main outcome measures: Annual population rates of death attributed to opioid dependence or accidental opioid poisoning in people aged 15-44 years, by sex and birth cohort tin five-year intervals, 1940-1944 to 1975-1979). Results: The rate of opioid overdose deaths increased 55-fold between 1964 and 1997, from 1.3 to 71.5 per million population aged 15-44 years. The rate of opioid overdose deaths also increased substantially over the eight birth cohorts, with an incidence rate ratio of 20.70 (95% confidence interval, 13.60-31.46) in the 1975-1979 cohort compared with the 1940-1944 cohort. The age at which the cumulative rate of opioid overdose deaths reached 300 per million fell in successive cohorts (for men, from 28 years among those born 1955-1959 to 22 years among those born 1965-1974; for women, from 33 years among those born 1955-1959 to 27 years among those born 1965-1969). Conclusions: Heroin use in Australia largely began in the early 1970s and rates of heroin use have markedly increased in birth cohorts born since 1950.

Women drivers' behaviour, socio-demographic characteristics and accidents

The purpose of this study was to examine factors which affect driving behaviour and accident rates in women in Australia. Two groups of women (aged 18-23 and 45-50 years) participating in the Australian Longitudinal Study on Women's Health, completed a mailed questionnaire on driver behaviour and road accidents. Self reported accident rates in the last 3 years were 1.87 per 100 000 km for the young drivers (n = 1199) and 0.59 per 100 000 km for the mid-age drivers (n = 1564); most accidents involved damage only, not injury. Mean scores for lapses obtained using the Driver Behaviour Questionnaire, were similar in the two age groups and similar to those found in other studies. In contrast, scores for errors and violations for the young women were higher than for the mid-age group and previous reports using the same instruments. Riskier driving behaviour among young women was associated with stress and habitual alcohol consumption. In the mid-age group, poorer driver behaviour scores were related to higher levels of education, feeling rushed, higher habitual alcohol consumption and lower life satisfaction scores. Accident rates in both groups were significantly related to lapses. Women born in non-English speaking countries had significantly higher risk of accidents compared to Australian-born women: relative risk = 3.40, 95% confidence interval (1.93, 5.98) for the young drivers; relative risk = 1.77, 95% confidence interval (1.11, 2.83) for mid-age drivers. These findings support the need for road safety campaigns targeted at young women to reduce dangerous driving practices, such as speeding,'tail gating' and overtaking on the inside. There is also a need for further research to understand how lifestyle characteristics are associated with higher risk of accidents and to explore factors which might account for the higher risk for women drivers who were born overseas. (C) 1999 Elsevier Science Ltd. All rights reserved.

Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa

Objective: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). Setting: Hlabisa, South Africa. Patients: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. Methods: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. Results: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P < 0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. Conclusion: Relapse rates are acceptably low following successful DOT with a twice weekly rifampifin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention. (C) 1999 Lippincott Williams & Wilkins.

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia

A population-based observational study of men acid women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact. of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chess pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than hall of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment. J CLIN EPIDEMIOL 52;8:761-771, 1999. (C) 1999 Elsevier Science Inc.

Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1393 (odds ratio [OR] 1.9, 95% confidence interval [CT] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95% CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95% CI 1.4-2.6); and male versus female sex (OR 1.3, 95% CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

Beyond ovulation: Oral contraceptives and epithelial ovarian cancer

In a case-control study in three Australian states that included 794 women with epithelial ovarian cancer and 853 community controls for whom we had adequate contraceptive and reproductive histories, Re examined the effects of oral contraceptive use after controlling for estimated number of ovulatory cycles. Other covariates included in the multiple logistic regression analysis were parity, smoking, and history of pelvic surgery. The protective effect of duration of oral contraceptive use appeared to be multiplicative, with a 7% decrease in relative risk per year [95% confidence interval (CI) = 4-9%], persisting beyond 15 years of exposure. Use for up to 1 year may have a greater effect than predicted (odds ratio = 0.57; 95% CI = 0.40-0.82), whereas use before the first pregnancy may be additionally beneficial (odds ratio = 0.95; 95% CI = 0.87-1.03, adjusted for overall duration of use). Better control for ovulatory life might attenuate these estimates somewhat. There was little evidence of waning protection with time since last exposure or of extra benefit with early commencement of oral contraceptive use. We found no convincing evidence of effect modification in any factor examined or differences in effect among the three main histologic cancer types or between borderline and malignant tumors. Oral contraceptives may act by both suppressing ovulation and altering the tumor-promoting milieu.

High HIV incidence and prevalence among young women in rural South Africa: Developing a cohort for intervention trials

Objective: To measure prevalence and model incidence of HIV infection. Setting: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. Methods: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. Results: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. in 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). Conclusions: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.

The serotonin transporter gene and Parkinson's disease

Dysfunction in the serotonin (5-hydroxytryptamine) system and reduced serotonin concentrations have been reported in patients with Parkinson's disease (PD). Serotonin concentrations in neural tissue are controlled by a presynaptic serotonin transporter protein that is encoded by a single gene. Therefore, we investigated whether a polymorphic region in the serotonin transporter gene is associated with PD. Three variable-number tandem repeat (VNTR) elements of the serotonin transporter gene were detected by polymerase chain reaction, those with 9, 10, 11 and 12 copies of the repeat element. The 10-copy VNTR element was significantly less common in patients with PD than controls in the univariate analysis (p < 0.05). Logistic regression analysis revealed no significant differences between patients (n = 198) and controls (n = 200) in the distribution frequencies of 9-and 12-copy alleles and combined genotypes (odds ratio = 1.20; p = 1.71). A positive family history of PD was a strong predictor of disease risk (odds ratio = 2.98; 95% confidence interval 1.51-5.87; p = 0.001). Although slight differences were observed between patient and control groups, these data suggest that defects in serotonin concentrations in patients with PD are unlikely to be due to polymorphisms in the serotonin transporter gene in this large Australian cohort; however, the inverse association observed with the 10-copy allele warrants further investigation. Copyright (C) 2000 S. Karger AG, Basel.