Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases.

The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.

Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics.

In a hospital-based case-control study, the risk of a first episode of major upper gastrointestinal tract bleeding in subjects now known to be predisposed was assessed in relation to the use of nonnarcotic analgesics. For aspirin use within the week before the onset of symptoms, the rate ratio estimates, adjusted for potential confounding, were 15 (95% confidence interval, 6.4 to 34) for regular use (at least four days a week) and 5.6 (confidence interval, 2.7 to 12) for occasional use. For aspirin use discontinued at least one week earlier, the estimate was 1.6 (confidence interval, 0.6 to 4.2). There was no evidence that acetaminophen use increased the risk. For the regular use of other analgesics in the week before onset, the adjusted rate ratio estimate was 9.1 (confidence interval, 2.7 to 31); there were insufficient data to evaluate occasional use. The findings suggest that the risk of bleeding is increased substantially by aspirin, even when used occasionally. With the exception of acetaminophen, other nonnarcotic analgesics may also increase the risk, but they remain to be evaluated individually.

Profiling high-range speeding offenders: investigating criminal history, personal characteristics, traffic offences, and crash history.

This paper reports profiling information for speeding offenders and is part of a larger project that assessed the deterrent effects of increased speeding penalties in Queensland, Australia, using a total of 84,456 speeding offences. The speeding offenders were classified into three groups based on the extent and severity of an index offence: once-only low-rang offenders; repeat high-range offenders; and other offenders. The three groups were then compared in terms of personal characteristics, traffic offences, crash history and criminal history. Results revealed a number of significant differences between repeat high-range offenders and those in the other two offender groups. Repeat high-range speeding offenders were more likely to be male, younger, hold a provisional and a motorcycle licence, to have committed a range of previous traffic offences, to have a significantly greater likelihood of crash involvement, and to have been involved in multiple-vehicle crashes than drivers in the other two offender types. Additionally, when a subset of offenders' criminal histories were examined, results revealed that repeat high-range speeding offenders were also more likely to have committed a previous criminal offence compared to once only low-range and other offenders and that 55.2% of the repeat high-range offenders had a criminal history. They were also significantly more likely to have committed drug offences and offences against order than the once only low-range speeding offenders, and significantly more likely to have committed regulation offences than those in the other offenders group. Overall, the results indicate that speeding offenders are not an homogeneous group and that, therefore, more tailored and innovative sanctions should be considered and evaluated for high-range recidivist speeders because they are a high-risk road user group.

Assessing specific deterrence effects of increased speeding penalties using four measures of recidivism.

Traffic law enforcement sanctions can impact on road user behaviour through general and specific deterrence mechanisms. The manner in which specific deterrence can influence recidivist behaviour can be conceptualised in different ways. While any reduction in speeding will have road safety benefits, the ways in which a 'reduction' is determined deserves greater methodological attention and has implications for countermeasure evaluation more generally. The primary aim of this research was to assess the specific deterrent impact of penalty increases for speeding offences in Queensland, Australia, in 2003 on two cohorts of drivers detected for speeding prior to and after the penalty changes were investigated. Since the literature is relatively silent on how to assess recidivism in the speeding context, the secondary research aim was to contribute to the literature regarding ways to conceptualise and measure specific deterrence in the speeding context. We propose a novel way of operationalising four measures which reflect different ways in which a specific deterrence effect could be conceptualised: (1) the proportion of offenders who re-offended in the follow up period; (2) the overall frequency of re-offending in the follow up period; (3) the length of delay to re-offence among those who re-offended; and (4) the average number of re-offences during the follow up period among those who re-offended. Consistent with expectations, results suggested an absolute deterrent effect of penalty changes, as evidenced by significant reductions in the proportion of drivers who re-offended and the overall frequency of re-offending, although effect sizes were small. Contrary to expectations, however, there was no evidence of a marginal specific deterrent effect among those who re-offended, with a significant reduction in the length of time to re-offence and no significant change in the average number of offences committed. Additional exploratory analyses investigating potential influences of the severity of the index offence, offence history, and method of detection revealed mixed results. Access to additional data from various sources suggested that the main findings were not influenced by changes in speed enforcement activity, public awareness of penalty changes, or driving exposure during the study period. Study limitations and recommendations for future research are discussed with a view to promoting more extensive evaluations of penalty changes and better understanding of how such changes may impact on motorists' perceptions of enforcement and sanctions, as well as on recidivist behaviour.

The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study.

A long-term retrospective follow-up study was performed to evaluate the risk of skin cancer in 1098 renal transplant recipients in Queensland, Australia. In a subgroup, we also assessed the influence of immunosuppressive therapy on the risk of developing skin cancer: cyclosporine alone or in combination with prednisolone; azathioprine alone or in combination with prednisolone; or the combination of cyclosporine and azathioprine with or without prednisolone. The cumulative incidence of developing skin cancer, calculated by life table analysis, increased progressively from 7% after 1 year of immunosuppression to 45% after 11 years and to 70% after 20 years of immunosuppression. Multivariate analysis in a subgroup comparing the risk of developing skin cancer in patients on either long-term cyclosporine or azathioprine (each with or without prednisolone) and in patients on the combination of cyclosporine and azathioprine (with or with- out prednisolone) showed no differences between the groups. We conclude that it is likely that the increased risk of skin cancer associated with immunosuppression is independent of the agent(s) used and is a result of the immunosuppression per se.

Diet and melanoma. An exploratory case-control study.

This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.

A ? developmental characteristic of the ultrastructure of childhood leukaemic lymphoblasts.

Areas of chromatin demarcated from the rest of the nucleus ("separations") were found frequently in acute lymphoblastic leukaemias of childhood, in some patients in apparently all leukaemic cells, but rarely in non-lymphocytic leukaemias. In normal lymphocytes, separations were most common in fetal thymus, and less frequent in fetal lymph node and bone marrow, and child thymus, lymph node and marrow. Separations may be a developmental marker, and fetal lymphoid tissues, especially thymus, may have significance in the origin of lymphoblastic leukaemias of childhood. Nuclear loops enclosing cytoplasmic material were associated with, and may have similar significance to, separations.

Estimating risks for matching factors in case-control studies.

Matching for factors such as age and sex is a convenient method for minimizing confounding in case-control studies, but it does not allow inferences about the effects of the matching factors unless case ascertainment is virtually complete and the distribution of the matching factors in the source population is known. When this is so, the effect of a particular factor can be estimated by comparing the population distribution of that factor with what is observed in the case series. Such a comparison, however, may itself be confounded by other factors that are related to both the matching factors and the disease under investigation. This article proposes a method for evaluating matching factors as risk factors, which uses information on the distribution of potential confounders in the reference series and exposure relative risk estimates to adjust the person-time proportionality constant in a Poisson regression model. The method is particularly suited to data sets in which many of the elementary matching strata contain few or no cases and/or controls. It makes use of standard analytic procedures, but requires the estimation of an additional variance-covariance component for the estimated Poisson regression coefficients. Further factors that may confound the relationship between exposure and disease are easily accommodated. The method is demonstrated in two examples: a matched case-control study of drugs in relation to the rare blood dyscrasia, agranulocytosis, that was conducted in Europe and Israel, and a case-control study of ovarian cancer in Australia.

Coronary heart disease mortality in Australia: is mortality starting to increase among young men?

BACKGROUND: There has been a major decline in mortality from coronary heart disease (CHD) in Australia from about 1967 through to 1989, occurring across all age groups simultaneously. We have analysed data up until 1992 to examine for trends within age cohorts. METHODS: Death registrations for acute myocardial infarction and CHD were used to construct male and female 5-year age- and cohort-specific mortality rates starting at 1900-1904 for cohorts and 25-29 years for age. Trends within age group and within cohort were compared across time. RESULTS: Across all female and most male birth cohorts there was a decrease in CHD mortality across the time period. In the youngest male cohorts there was a significant flattening in the rate of decline in the most recent periods. Comparison of age-specific mortality across cohorts showed the mortality at any period to be lower in the most recent cohort. CONCLUSIONS: This analysis demonstrates a continuing decline in mortality from CHD among females of all ages in Australia although the rate of decline appears to have slowed or even ceased in younger males.

Evaluation of haptoglobin phenotype 0-0 in cirrhotic and non-cirrhotic hospital populations.

The haptoglobin phenotypes of 3,332 individuals, consisting of 2,930 caucasians and 402 negroes living in the greater Boston area, were determined. Of these, 3,222 were hospitalized medical patients fully documented regarding diagnoses. One hundred and twentyeight of the total population studied were shown to exhibit starch gel anhaptoglobinaemia (3.7%). Re-evaluation on acrylamide gel of 118 0-0 samples revealed that the majority (94%) were derived from patients exhibiting hypohaptoglobinaemia rather than anhaptoglobinaemia.

Patient and health care system delays in Queensland tuberculosis patients, 1985-1998.

SETTING: Queensland tuberculosis (TB) control centre QTCC). OBJECTIVE: To investigate patient and health care system delays in the diagnosis of active TB in Queensland. DESIGN: Analysis of data extracted from the QTCC database and review of charts. Symptomatic patients with bacteriologically or histologically proven TB were considered as a total group and a pulmonary smear-positive (PSP) group. RESULTS: The median patient delays were 29 days (total group) and 30 days (PSP group). The median health care system delays were 22 days (total group) and 11 days (PSP group). There were significant trends towards increasing health care system delays with increasing age and longer residency of migrants in Australia. Health care system delays were significantly longer for females and those aged over 45. Migrants from countries of high TB incidence and indigenous Australians had shorter health care system delays compared to non-indigenous Australians. Common reasons for diagnostic delays of more than 90 days were failure to perform appropriate investigations and misdiagnosis of chest X-rays. CONCLUSION: Physicians need to consider including TB in the differential diagnosis in older age groups and migrants with longer residency in Australia. There should be a low threshold for obtaining chest X-rays and sputum samples in patients with persistent cough.

Tuberculosis-related deaths in Queensland, Australia, 1989-1998: characteristics and risk factors.

OBJECTIVE: To review factors associated with TB-related deaths in Queensland, Australia. DESIGN: Review of data for TB patients dying before treatment completion; demographic and clinico-pathological comparison of TB-related deaths with other notified patients after exclusion of losses to follow-up; matched case-control study of co-morbid conditions in patients under 75 years. RESULTS: Of 1003 tuberculosis cases notified between 1989 and 1998, 127 died before completing anti-tuberculosis treatment. Tuberculosis was the main cause of death in 53 cases, a significant contributor in 34 and unrelated in 40, giving a TB-related case fatality rate of 8.7%. Decedents were older on average, except among indigenous Australians (IA); age-adjusted case fatality rates did not vary significantly among ethnic groups. Pulmonary and disseminated TB, coexistent malnutrition, renal disease and liver disease increased the risk of death. HIV infection increased the risk of dying, but was uncommon among Queensland cases. Neither sputum smear positivity nor drug resistance was associated with risk of death. Twenty-five TB-related deaths occurred before diagnosis, with significant overrepresentation of IA. Most had serious co-morbidities and symptomatic pulmonary disease. Seven socially or geographically isolated decedents did not access documented health care for tuberculosis. CONCLUSIONS: Fatality was related to older age, disseminated disease and co-morbidity. Dying undiagnosed from tuberculosis was associated with respiratory co-morbidity and social and geographical isolation, mainly in the aged in low TB risk populations and in IA in remote regions.

The incidence of melanocytic naevi in adolescent children in Queensland, Australia.

The aim of this study was to assess longitudinally the development of melanocytic naevi in children around the time of their puberty. In Queensland, Australia, 102 schoolchildren born mostly in 1977 or 1978, were examined annually on four occasions from 1990. All naevi on the body except for the scalp and parts covered by a bathing suit were counted by an experienced research nurse or trained assistant according to a set protocol. In addition, each subject's pigmentary characteristics were recorded and height, weight and pubertal status were assessed annually. The findings confirmed that the average number of naevi and average density of naevi (count per m2) on the whole body in boys and girls increase significantly with increasing age and increases were also seen on each of the following anatomic sites: face and neck, back and shoulders, and upper and lower limbs. Children who had a high baseline naevus count, or a large increase in skin surface area during the 3-year follow-up period had the highest absolute increases in naevus count but the smallest proportionate increases. Associations between baseline naevus counts and male sex, light brown or blonde hair, blue or hazel eyes, facial freckling and a tendency to sunburn, which have been previously reported, were also found. However, the independent relations of each of these factors to the increase in new naevi were more complex, once the effects of high naevus counts at baseline and increases in skin surface area were taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of hospital discharge in immediate survivors of ventricular fibrillation or asystole.

Survival from ventricular fibrillation and asystole is influenced by variables measured during resuscitation that affect both immediate survival and discharge from hospital. These variables have been used to develop a formula to calculate an individuals chances of immediate survival and hospital discharge. It has allowed this heterogenous group to be subdivided into groups which can be compared both within and between institutions for the purposes of audit and evaluation of resuscitation protocols. This study evaluates the addition of clinical parameters to the prognostic index. One hundred twelve immediate survivors of ventricular fibrillation or asystole were examined immediately after resuscitation and clinical parameters measured and recorded. At the same time parameters previously described were recorded. The increase in the numbers of survivors improved the reliability (area under the receiver operator curve (ROC) improved from 0.79 to 0.83) of the index for predicting hospital discharge. Addition of the clinical variables of conscious state, respiratory state, blood pressure and pulse rate improved the prognostic index further to an ROC area of 0.86. This ensures that the predictive power of the new index is now highly reliable for predicting hospital discharge after successful resuscitation from ventricular fibrillation and asystole.

Prediction of survival from resuscitation: a prognostic index derived from multivariate logistic model analysis.

Despite advances in resuscitation, the ability to predict survival at cardiac arrests remains unsophisticated. We identified the factors determining outcome of all cardiopulmonary resuscitations performed at our institution over a 4-year period, and used a Cox multivariate regression model to design prognostic indices to assess the probability of successful resuscitation and hospital discharge. Cardiac arrests (710) were studied, and 193 (28%) were successfully resuscitated. The most influential variables, judged by the size and significance of their logistic regression coefficients, were rhythm, resuscitation delay, and age (for successful resuscitation), and rhythm, performance of intubation and defibrillation, defibrillation delay, and age (for survival until discharge). The combination of these in a prognostic index reliably predicted both outcome (area under the receiver operating curve of 0.78), and survival until discharge (area under the curve of 0.80).

Viral-like characteristics of particle aggregates in a lymphoblastic cell line.

A lymphoblastic cell line (K45) established from a child with acute lymphoblastic leukemia (ALL) is characterized by a profusion of intracytoplasmic particle aggregates (PA) similar in morphology to those occurring in fresh childhood ALL cells. The PA in K45 cells were examined for morphology and capacity for nucleic acid synthesis to test the hypothesis that they are identical to those in fresh ALL cells, and also to identify characteristics which might distinguish PA from cell organelles and which might determine if they are viral-like. In contrast to cell organelles, the PA in both K45 and ALL cells were found to be characterized by a localized thickening of the particle wall. Furthermore, autoradiography of K45 cells showed uptake by PA of 3H uridine rather than 3H thymidine indicating an RNA composition. The presence of PA in profusion was associated with, but preceded necrotic death of K45 cells. These combined features suggest that the PA in K45 and in ALL cells are identical, that they are distinct from cell organelles, are not formed as a consequence of the initiation of cell death and that, while their exact nature remains unknown, a viral origin cannot be excluded.

Do psycho-social factors contribute more to symptom reporting by middle-aged women than hormonal status?

Six hundred women aged between 45 and 54 were randomly selected from the electoral roll in Brisbane, Australia. A questionnaire addressing their symptoms, hormone status and psycho-social factors was successfully administered to 381 women (64% of the original sample; 83% of those contactable). Although cardiovascular symptoms were experienced by 25% of the sample, the most common (hot flushes) ranked only tenth on a list of recently experienced symptoms. The association of hormone status with symptoms was weak in comparison with other factors. Most symptoms were reported by women who were perimenopausal, had undergone a hysterectomy, or were currently using hormone replacement therapy. A poor mental health index was strongly associated with all groups reporting symptoms. It is concluded that clinicians responding to symptoms from middle-aged women should continue to address psychosocial factors just as vigorously as those related to their hormone status.

Validity of self-reported hysterectomy and tubal sterilisation. The Survey of Women's Health Study Group.

Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self-reports of these procedures, we assessed their reliability and validity using data obtained in a case-control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self-reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long-term effects of these procedures to be studied with reasonable accuracy from self-reports.

Does license disqualification reduce reoffence rates?

A review was conducted of the subsequent driving records of over 25,000 Queensland drivers cited for a drink driving offence in 1988 who received at least one subsequent license restriction. The interval of follow-up was at least 3 years, average 3.9 years. Periods of driving disqualification were identified and, for each driver, the total amount of time during restricted and unrestricted driving was computed; the numbers of events, i.e. crashes and traffic offences, recorded during these periods were counted. Rates under disqualification and during legal driving, expressed per thousand person-years were derived by dividing total numbers of events by total time during which they could occur. Three categories of traffic violation were considered: drink driving offences; traffic offences unassociated with drink driving, and any offence involving driving. Since only 12% of the offenders and 9% of the reoffenders were female, detailed analyses are presented for men only; results for women were little different. Statistical inference assumed a Poisson model for crashes and a negative binomial model for offences, and analyses were performed after stratification by number of drink driving offences. Calculated rates during periods of disqualification were about one third of the rates during legal driving for crashes and all three categories of traffic offence, ranging from 25% in the case of unassociated offences to 35% for any driving offence. There were differences, some statistically significant, by age and between metropolitan, provincial city and rural regions of the State, but most were relatively minor. Drivers were apprehended more frequently earlier in the disqualification period than later. It is impossible from these data to distinguish between reduced driving levels and more cautious traffic behaviour during periods of license restriction. It is nonetheless clear that while such penalties are in operation, they substantially reduce the negative impact of convicted drink-drivers on the road. Unfortunately the data do not permit one to say whether or for how long the effect persists.

Validating the process of taking lateral foot x-rays.

This study validates the concept that a standard (static) weightbearing lateral x-ray, taken with an orthoposer device, in the patient's angle and base of gait is clinically similar to findings seen during ambulatory (dynamic) gait. Sixty female subjects requiring diagnostic x-rays underwent videofluoroscopy of their walking gait. Using a single-frame, shuttle-advance video recorder, the appropriate fluoroscopic video frame was identified. The calcaneal pitch angle was measured using a digitized program. A high repeatability of the measuring process and high correlation between x-ray and fluoroscopic results suggest the value of taking weightbearing angle and base of gait lateral x-rays.