Philip Ryan

Role of medical history in brain tumour development. Results from the international adult brain tumour study

In an international population‐based case‐control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age‐ and gender‐matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti‐epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation. Int. J. Cancer82:155–160, 1999.

The Effect of Heat Waves on Mental Health in a Temperate Australian City

Objective The goal of this study was to identify mental, behavioral, and cognitive disorders that may be triggered or exacerbated during heat waves, predisposing individuals to heat-related morbidity and mortality. Design Using health outcome data from Adelaide, South Australia, for 1993–2006, we estimated the effect of heat waves on hospital admissions and mortalities attributed to mental, behavioral, and cognitive disorders. We analyzed data using Poisson regression accounting for overdispersion and controlling for season and long-term trend, and we performed threshold analysis using hockey stick regression. Results Above a threshold of 26.7°C, we observed a positive association between ambient temperature and hospital admissions for mental and behavioral disorders. Compared with non–heat-wave periods, hospital admissions increased by 7.3% during heat waves. Specific illnesses for which admissions increased included organic illnesses, including symptomatic mental disorders; dementia; mood (affective) disorders; neurotic, stress related, and somatoform disorders; disorders of psychological development; and senility. Mortalities attributed to mental and behavioral disorders increased during heat waves in the 65- to 74-year age group and in persons with schizophrenia, schizotypal, and delusional disorders. Dementia deaths increased in those up to 65 years of age. Conclusion Our results suggest that episodes of extreme heat pose a salient risk to the health and well-being of the mentally ill. Relevance to Clinical or Professional Practice: Improvements in the management and care of the mentally ill need to be addressed to avoid an increase in psychiatric morbidity and mortality as heat waves become more frequent.

Diet, acetylator phenotype, and risk of colorectal neoplasia

BACKGROUND Inherited or acquired differences in metabolic pathways that activate or inactivate dietary carcinogens may influence the risk of developing cancer. A polymorphism in N-acetyltransferase classified people into fast and slow acetylators. This enzyme catalyses the formation of mutagenic products from foodstuffs, especially cooked meat and fish. Some data suggest that fast acetylators are at higher risk of colorectal cancer. We have studied the adenoma and cancer risk in relation to meat intake and acetylator status. METHODS In a case-control study, we compared 110 patients with colorectal cancer, 89 patients with colorectal adenomatous polyps, and 110 controls. Acetylator status was assessed by the rate of acetylation of sulphamethazine given orally. FINDINGS The fast-acetylator phenotype was associated with odds ratios of 1.1 (95% Cl 0.6-2.1) and 1.8 (1.0-3.3) for adenoma and colorectal cancer, respectively. The highest risk occurred in the youngest tertile (< 64 years) of cases (2.5 [0.7-9.4] and 8.9 [2.6-30.4], respectively). There was no difference between the sexes. The risk of adenoma or cancer increased with increasing intake of meat in fast but not in slow acetylators: covariate-adjusted odds of disease over three levels of meat consumption were 2.1 (0.9-4.7) for adenoma, 1.7 (0.9-3.5) for cancer, and 1.9 (1.0-3.7) for all tumours. INTERPRETATION Our findings indicate that acetylator status modulates the risk of colorectal neoplasia associated with meat intake.

Brachial Blood Pressure But Not Carotid Arterial Waveforms Predict Cardiovascular Events in Elderly Female Hypertensives

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease–free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88±12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease–free survival (hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure ≥81 versus <81 mm Hg; P=0.01), no such relation was found for carotid augmentation index (HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance (HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study.

Objective:The aim of this pilot study was to assess any trends related to the timing of initiation, and duration, of hormone therapy (HT) use on cognitive function to facilitate the design and power calculations for a future large cohort study entitled Research into Memory, Brain function and Estrogen Replacement (REMEMBER). Design:A total of 428 women aged older than 60 years were recruited from a computer-generated random selection of Adelaide households. Demographic and lifestyle characteristics, and HT use history were recorded and confirmed. The Center for Epidemiological Studies-Depression score was used to assess mood. Cognitive tests were administered measuring global cognition (Mini-Mental State Examination), attention and concentration (Trail Making Test Parts A and B), verbal learning and memory (Consortium to Establish a Registry for Alzheimers Disease [CERAD] word list immediate and delayed recall), and verbal expression (letter fluency [FAS], category fluency [Animals], and the Boston Naming Test [short form]). Analyses were adjusted for age, education, mood, body mass index, smoking, alcohol intake, and history of cerebrovascular disease. HT use was defined as the use of systemic HT for at least 1 year. Early initiation of HT use was defined as commencement of HT before age 56 years for women with a uterus and ovaries, or within 5 years of a hysterectomy and bilateral oophorectomy. Late initiation of HT use was defined as HT commencing after these times. Results:Early initiators of HT performed better than late initiators on the Mini-Mental State Examination (P = 0.04) and were faster than never users on the Trail Making Test Part A (P = 0.02). Women aged 70-79 years who initiated HT early performed better on the FAS test than never users (P = 0.0008). Late initiators performed worse than never users on the Mini-Mental State Examination (P = 0.09), and on the FAS test in the 60-69 year (P = 0.06) and 80 years and older (P = 0.095) age groups. However, late initiators performed better than never users on the FAS test in the 70-79 year age group (P = 0.015). HT users of less than 11 years (P = 0.09), HT users of more than 11 years (P = 0.04), and estrogen-only users (P = 0.024) performed faster than never users on the Trail Making Test Part A. Combined estrogen plus progestin users performed better than never users on the Boston Naming Test short form (P = 0.07). Conclusions:For some cognitive domains, early initiation of HT from around menopause may be beneficial, and initiation of HT in late menopause may be detrimental. The timing of the initiation of HT seems critical. To fully test these hypotheses and to further examine these trends by route and type of HT regimen in this population, a study size of 2,500 women would be required.

Performance of the Modified Poisson Regression Approach for Estimating Relative Risks From Clustered Prospective Data

Modified Poisson regression, which combines a log Poisson regression model with robust variance estimation, is a useful alternative to log binomial regression for estimating relative risks. Previous studies have shown both analytically and by simulation that modified Poisson regression is appropriate for independent prospective data. This method is often applied to clustered prospective data, despite a lack of evidence to support its use in this setting. The purpose of this article is to evaluate the performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data, by using generalized estimating equations to account for clustering. A simulation study is conducted to compare log binomial regression and modified Poisson regression for analyzing clustered data from intervention and observational studies. Both methods generally perform well in terms of bias, type I error, and coverage. Unlike log binomial regression, modified Poisson regression is not prone to convergence problems. The methods are contrasted by using example data sets from 2 large studies. The results presented in this article support the use of modified Poisson regression as an alternative to log binomial regression for analyzing clustered prospective data when clustering is taken into account by using generalized estimating equations.

Risk Factors for Revision for Early Dislocation in Total Hip Arthroplasty

Risk factors were investigated for revision for dislocation in primary total hip arthroplasties (THAs) between September 1, 1999, and December 31, 2004, as reported by the Australian Orthopaedic Association National Joint Replacement Registry. For 65992 primary THAs, the only initial diagnoses with significantly increased relative risk (RR) of revision for dislocation compared to osteoarthritis were fractured neck of femur (RR, 2.03; P < .001), rheumatoid arthritis (RR, 2.01; P < .01), and avascular necrosis (RR, 1.57; P < .05). A total of 58109 primary THAs for osteoarthritis were investigated for effect of age group, sex, and fixation method. There were 428 (0.7%) revisions for dislocation, 369 (0.8%) with a cementless acetabulum, and 59 (0.6%) with cemented acetabulum (RR, 1.59; P < .01). There is a significantly increasing risk of revision for dislocation as head size decreases (P < .001). Cementless acetabula, particularly with smaller heads, have a higher rate of revision for dislocation.

A cross-sectional survey to assess community attitudes to introduction of Human Papillomavirus vaccine

Objective: A vaccine to prevent human papilloma virus (HPV) infection has been licensed recently in the United States of America and Australia. The aim of this study was to assess community attitudes to the introduction of HPV vaccine in the State of South Australia.

Polymorphism in alcohol‐metabolizing enzymes, glutathione S‐transferases and apolipoprotein E and susceptibility to alcohol‐induced cirrhosis and chronic pancreatitis

Background and Aim Susceptibility to organ damage induced by alcohol may be due to inherited variation (polymorphism) in ethanol‐metabolizing enzymes, or to polymorphisms affecting free radical or lipid metabolism mediated by enzymes such as glutathione S‐transferases and apolipoprotein E. The aim was to compare the genotype frequencies of alcohol dehydrogenase‐2 (ADH2), ADH3, aldehyde dehydrogenase‐2 (ALDH2), cytochrome P450‐2E1 (CYP2E1), glutathione S‐transferase‐M1 (GSTM1), GSTT1, and apolipoprotein E in patients with alcoholic cirrhosis and alcoholic chronic pancreatitis to those in control groups.

The importance of immediate cooling—a case series of childhood burns in Vietnam

Numerous experimental studies have shown several benefits of treating burns by the immediate application of cool water. In this study of 695 children with burns, treated in the National Burn Institute (NBI), Hanoi, Vietnam, patients were assessed on admission according to first aid measures at the time of injury, i.e. the removal of the cause and immediate cooling with cold water. A total of 33% of the children who had had immediate cooling of the burn with water had deep burns, compared with 49% of the children who had not had immediate cooling. The prevalence ratio of deep burns was thus 0.68 (95% confidence interval (CI) 0.55-0.85); that is, there was an estimated reduction of 32% in the need for skin grafting, a reduction which was statistically significant. After adjusting for the effect of cooling the burn, removal of the causal agent reduced the odds of requiring skin grafting, but the reduction was not statistically significant. It is concluded that early cooling will prevent a significant percentage of superficial burns from progressing to deep burns. This will not only reduce the probability that skin grafting and expensive treatment will be required, but will reduce the risk of other consequences of deep burns, which may be fatal. Public health programs to promote immediate cooling of burns with cool water are at least as important as subsequent medical and surgical treatment in determining the outcome of burns in children.