General Practice and Primary Care - Research Publications
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ItemHistopathologic indicators of breast cancer biology: insights from population mammographic screening(NATURE PUBLISHING GROUP, 2005-04-25)Histopathologic features of breast cancer such as tumour size, grade and axillary lymph node (LN) status variably reflect tumour biology and time. Recent evidence suggests that the biological character of breast cancer is established at an early stage and has a major impact on clinical course. The aim of this study was to distinguish the impact of biology on breast cancer histopathology by comparing features of breast cancers diagnosed following population mammographic screening with prevalent vs incident detection and screening interval. Central histopathology review data from 1147 cases of ductal in situ and/or invasive breast cancer were examined. Size, grade and LN status of invasive cancers were positively correlated (P < 0.001). Prevalent invasive cancers were larger (P < 0.001) and more likely to be LN positive (P = 0.02) than incident cases, but grade was not associated with screening episode (P = 0.7). Screening interval for incident cancers was positively associated with invasive cancer size (P = 0.05) and LN status (P = 0.002) but not grade (P = 0.1). Together, these data indicate that biology and time both impact on size and LN status of invasive breast cancer, but grade reflects biology alone. In view of the clinical importance of breast cancer biology, grade as its most direct indicator assumes particular significance.
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ItemADRENERGIC FACTORS REGULATING CELL-DIVISION IN THE COLONIC CRYPT EPITHELIUM DURING CARCINOGENESIS AND IN COLONIC ADENOMA AND ADENOCARCINOMA(SPRINGERNATURE, 1985)Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.
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ItemNo Preview AvailableMale preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPP1R3A locus -: art. no. 11(BIOMED CENTRAL LTD, 2003-06-28)BACKGROUND: The ARE insertion/deletion polymorphism of PPP1R3A has been associated with variation in glycaemic parameters and prevalence of diabetes. We have investigated its role in age of diagnosis, body weight and glycaemic control in 1,950 individuals with type 2 diabetes in Tayside, Scotland, and compared the ARE2 allele frequencies with 1,014 local schoolchildren. RESULTS: Men homozygous for the rarer allele (ARE2) were younger at diagnosis than ARE1 homozygotes (p = 0.008). Conversely, women ARE2 homozygotes were diagnosed later than ARE1 homozygotes (p = 0.036). Thus, men possessing the rarer (ARE2) allele were diagnosed with type 2 diabetes earlier than women (p < 0.000001). In contrast, there was no difference in age of diagnosis by gender in those individuals carrying only the common ARE1 variant. Furthermore, although there was no difference in the frequency between the children and the type 2 diabetic population overall, marked differences in allele frequencies were noted by gender and age-of diagnosis. The ARE2 allele frequency in early diagnosed males (diagnosed earlier than the first quartile of the overall ages at diagnosis) was higher than that found in both later diagnosed males and healthy children (p = 0.021 and p = 0.03 respectively). By contrast, the frequency in early diagnosed females was significantly lower than later diagnosed females and that found in children (p = 0.021 and p = 0.037). Comparison of the male to female ratios at different ages-diagnosed confirms a known phenomenon that men are much more prone to early type 2 diabetes than women. When this feature was examined by the common ARE 1/1 genotype we found that the male to female ratio remained at unity with all ages of diagnosis, however, carriers of the ARE2 variant displayed a marked preponderance of early male diagnosis (p = 0.003). CONCLUSION: The ARE2 allele of PPP1R3A is associated with a male preponderance to early diagnosed type 2 diabetes. Susceptibility to type 2 diabetes in later life is not modulated by the ARE2 allele in either sex.
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ItemNo Preview AvailableHaplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight -: art. no. 21(BMC, 2002-11-13)BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight.
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ItemNo Preview AvailablePatients' preferences for involvement in treatment decision making in Japan.(Springer Science and Business Media LLC, 2004-03-01)BACKGROUND: A number of previous studies have suggested that the Japanese have few opportunities to participate in medical decision-making, as a result both of entrenched physician paternalism and national characteristics of dependency and passivity. The hypothesis that Japanese patients would wish to participate in treatment decision-making if adequate information were provided, and the decision to be made was clearly identified, was tested by interview survey. METHODS: The subjects were diabetic patients at a single outpatient clinic in Kyoto. One of three case study vignettes (pneumonia, gangrene or cancer) was randomly assigned to each subject and, employing face-to-face interviews, the subjects were asked what their wishes would be as patients, for treatment information, participation in decision-making and family involvement. RESULTS: 134 patients participated in the study, representing a response rate of 90%. The overall proportions of respondents who preferred active, collaborative, and passive roles were 12%, 71%, and 17%, respectively. Respondents to the cancer vignette were less likely to prefer an active role and were more likely to prefer family involvement in decision-making compared to non-cancer vignette respondents. If a physician's recommendation conflicted with their own wishes, 60% of the respondents for each vignette answered that they would choose to respect the physician's opinion, while few respondents would give the family's preference primary importance. CONCLUSIONS: Our study suggested that a majority of Japanese patients have positive attitudes towards participation in medical decision making if they are fully informed. Physicians will give greater patient satisfaction if they respond to the desire of patients for participation in decision-making.
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ItemNo Preview AvailableThe PAV trial: does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277].(Springer Science and Business Media LLC, 2004-03-28)BACKGROUND: Complementary and alternative medicines are used by many consumers, and increasingly are being incorporated into the general practitioner's armamentarium. Despite widespread usage, the evidence base for most complementary therapies is weak or non-existent. Post-antibiotic vulvovaginitis is a common problem in general practice, for which complementary therapies are often used. A recent study in Melbourne, Australia, found that 40% of women with a past history of vulvovaginitis had used probiotic Lactobacillus species to prevent or treat post-antibiotic vulvovaginitis. There is no evidence that this therapy is effective. This study aims to test whether oral or vaginal lactobacillus is effective in the prevention of post-antibiotic vulvovaginitis. METHODS/DESIGN: A randomised placebo-controlled blinded 2 x 2 factorial design is being used. General practitioners or pharmacists approach non-pregnant women, aged 18-50 years, who present with a non-genital infection requiring a short course of oral antibiotics, to participate in the study. Participants are randomised in a four group factorial design either to oral lactobacillus powder or placebo and either vaginal lactobacillus pessaries or placebo. These interventions are taken while on antibiotics and for four days afterwards or until symptoms of vaginitis develop. Women self collect a vaginal swab for culture of Candida species and complete a survey at baseline and again four days after completing their study medications. The sample size (a total of 496--124 in each factorial group) is calculated to identify a reduction of half in post-antibiotic vulvovaginitis from 23%, while allowing for a 25% drop-out. An independent Data Monitoring Committee is supervising the trial. Analysis will be intention-to-treat, with two pre-specified main comparisons: (i) oral lactobacillus versus placebo and (ii) vaginal lactobacillus versus placebo.
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ItemNo Preview AvailablePRISM (Program of Resources, Information and Support for Mothers) Protocol for a community-randomised trial [ISRCTN03464021](BMC, 2003-11-20)BACKGROUND: In the year after birth one in six women has a depressive illness, and 30% are still depressed, or depressed again, when their child is 2 years old, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support overall, more negative life events, and poorer physical health. Their perceptions of factors contributing to depression are lack of support, isolation, exhaustion and physical health problems. Fewer than one in three affected women seek help in primary care despite frequent contacts. METHODS/DESIGN: PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners' response to these issues, and through community-based strategies to develop broader family and community supports for recent mothers. Eligible local governments will be recruited and randomised to intervention or comparison arms, after stratification (urban/rural, size, birth numbers, extent of community activity), avoiding contiguous boundaries. Maternal depression and physical health will be measured six months after birth, in a one year cohort of mothers, in intervention and comparison communities. The sample size to detect a 20% relative reduction in depression, adjusting for cluster sampling, and estimating a population response fraction of 67% is 5740 x 2. Analysis of the physical and mental health outcomes, by intention to treat, will adjust for the correlated structure of the data.
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ItemObserved intra-cluster correlation coefficients in a cluster survey sample of patient encounters in general practice in Australia.(Springer Science and Business Media LLC, 2004-12-22)BACKGROUND: Cluster sample study designs are cost effective, however cluster samples violate the simple random sample assumption of independence of observations. Failure to account for the intra-cluster correlation of observations when sampling through clusters may lead to an under-powered study. Researchers therefore need estimates of intra-cluster correlation for a range of outcomes to calculate sample size. We report intra-cluster correlation coefficients observed within a large-scale cross-sectional study of general practice in Australia, where the general practitioner (GP) was the primary sampling unit and the patient encounter was the unit of inference. METHODS: Each year the Bettering the Evaluation and Care of Health (BEACH) study recruits a random sample of approximately 1,000 GPs across Australia. Each GP completes details of 100 consecutive patient encounters. Intra-cluster correlation coefficients were estimated for patient demographics, morbidity managed and treatments received. Intra-cluster correlation coefficients were estimated for descriptive outcomes and for associations between outcomes and predictors and were compared across two independent samples of GPs drawn three years apart. RESULTS: Between April 1999 and March 2000, a random sample of 1,047 Australian general practitioners recorded details of 104,700 patient encounters. Intra-cluster correlation coefficients for patient demographics ranged from 0.055 for patient sex to 0.451 for language spoken at home. Intra-cluster correlations for morbidity variables ranged from 0.005 for the management of eye problems to 0.059 for management of psychological problems. Intra-cluster correlation for the association between two variables was smaller than the descriptive intra-cluster correlation of each variable. When compared with the April 2002 to March 2003 sample (1,008 GPs) the estimated intra-cluster correlation coefficients were found to be consistent across samples. CONCLUSIONS: The demonstrated precision and reliability of the estimated intra-cluster correlations indicate that these coefficients will be useful for calculating sample sizes in future general practice surveys that use the GP as the primary sampling unit.
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ItemNo Preview AvailableDoctors' health-seeking behaviour: a questionnaire survey(AUSTRALASIAN MED PUBL CO LTD, 2003-09-15)OBJECTIVES: To explore doctors' perceptions of the acceptable limits to self-treatment and to identify barriers to doctors seeking appropriate healthcare. DESIGN: Self-completion, postal survey using three hypothetical case vignettes. SETTING AND PARTICIPANTS: 896 Australian doctors randomly selected from the Health Insurance Commission database and stratified by sex, discipline (general practitioner or specialist) and location (urban or rural). Data were collected between May and July 2001. MAIN OUTCOME MEASURES: Doctors' self-reported attitudes on illness behaviour and choice of medical care in response to case vignettes. RESULTS: 358 (40%) doctors returned questionnaires. More participants believed it was acceptable to self-treat acute conditions (315/351; 90%) than to self-treat chronic conditions (88/350; 25%). Nine per cent (30/351) of participants believed it was acceptable to self-prescribe psychotropic medication. A greater proportion of GPs (206/230; 90%) than specialists (101/121; 83%) believed doctors are reluctant to attend another doctor, especially if the problem is psychological. Women and GPs were significantly less likely to report that it was easy to find a satisfactory treating doctor (women, 58/140 [41%]; men, 128/211 [61%]; GPs, 106/231 [46%]; specialists, 80/120 [67%]). Being a specialist was predictive of seeking appropriate healthcare for all three vignettes. CONCLUSION: Doctors have varying opinions regarding the acceptability of self-treating chronic conditions, and perceive considerable barriers to seeking appropriate medical care. Strategies are needed to challenge the culture of self-reliance.
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ItemNo Preview AvailableThe general health status of people with mental illness(SAGE Publications, 2000-05-03)