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Biomedical subjects

D Gunnell

Publications and source records attributed to D Gunnell.

At least 19 recordsLinked to original sources

Associations of adult measures of childhood growth with breast cancer: findings from the British Women's Heart and Health Study.

Since the two components of adult height - leg length and trunk length - are poorly correlated with each other and appear to be influenced by different early life factors, examining their separate influence on breast cancer may provide additional insights into the mechanisms responsible for the positive association between adult height and breast cancer. In a cross-sectional study of 4286 women aged 60-79 years, in whom there were 170 cases of breast cancer, we found total height, leg length and trunk length were all modestly positively and linearly associated with breast cancer. The magnitudes of the associations of leg and trunk length were similar: fully adjusted odds ratio (95% confidence interval) of breast cancer for a one standard deviation (s.d.) increase in leg length 1.17 (0.98, 1.39) and for a 1 s.d. increase in trunk length 1.19 (0.99, 1.41). Self-reported birth weight (available on 33% of the sample) was positively and linearly associated with breast cancer: fully adjusted odds ratio of breast cancer for a 1 s.d. increase in birth weight 1.30 (0.93, 1.80). These associations were all independent of each other and other potential confounding factors and are likely to reflect different mechanisms by which factors operating prenatally and prepubertally influence breast cancer risk.

Aged↗

Are diet-prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-I and IGFBP-3 in healthy middle-aged men.

We examined the association of diet with insulin-like growth factors (IGF) in 344 disease-free men. Raised levels of IGF-I and/or its molar ratio with IGFBP-3 were associated with higher intakes of milk, dairy products, calcium, carbohydrate and polyunsaturated fat; lower levels with high vegetable consumption, particularly tomatoes. These patterns support the possibility that IGFs may mediate some diet-cancer associations.

Adult↗

Association between psychotic disorder and urban place of birth is not mediated by obstetric complications or childhood socio-economic position: a cohort study.

BACKGROUND: Although urban place of birth has been identified as a risk factor for schizophrenia, the extent to which this association is mediated by socially patterned risk factors such as obstetric complications and childhood socio-economic position is unclear. The diagnostic specificity of the association within the clinical psychotic syndromes is also unclear. METHOD: A population cohort of 696025 males and females, born in Sweden between 1973 and 1980 and with linked birth and socio-economic data was followed up from age 16 for up to 9.8 years. Hospitalized cases of schizophrenia and other non-affective psychosis were identified from the Swedish Inpatient Discharge Register. We examined associations of these disorders with a three-level measure of urbanicity of birthplace before and after controlling for measures of foetal nutrition, obstetric complications and level of maternal education. RESULTS: Urban compared to rural birthplace was associated both with increased risk of adult onset schizophrenia (hazard ratio 1.34, CI 0.91-1.96) and other non-affective psychoses (hazard ratio 1.63, CI 1.18-2.26). None of these associations was greatly affected by adjustment for obstetric complications or maternal educational level. In the group of other non-affective psychoses urban-rural differences in disease risk were strongest among those born in the winter months. CONCLUSION: Urbanization of birthplace is associated with increased risk of non-affective psychosis but this is not confined to narrowly defined cases. The magnitude of the association in Sweden is lower than that reported in other studies. Causal factors underlying this association appear to operate independently of risks associated with obstetric complications and parental educational status.

Adolescent↗

Trends in body mass index from 1948 to 1968: results from the Glasgow Alumni Cohort.

Most published studies suggest that the rising prevalence of overweight and obesity is a recent phenomenon. We have investigated whether secular trends in body mass index (BMI) existed in the 1950s and 1960s, using data collected from young adults attending Glasgow University. Mean BMI increased from 1948 to 1968 in men, and decreased slightly in women. The proportion of men who were overweight increased, whereas that of women changed little. These data must be interpreted in light of the fact that the study participants were relatively affluent, and not representative of the whole population in terms of socioeconomic position in childhood. The increases of BMI in men evident from 1948 to 1968 suggest that recent changes in exercise and dietary patterns do not fully explain changes in body weight over time.

Adolescent↗

An investigation of fetal, postnatal and childhood growth with insulin-like growth factor I and binding protein 3 in adulthood.

OBJECTIVE: Weight at birth and adult height are positively associated with cancer risk. These patterns may be mediated by the insulin-like growth factor (IGF) axis. We have examined whether pre- and postnatal growth patterns have a long-term influence on adult IGF-I and IGFBP-3 levels. DESIGN: A follow-up study of a randomized controlled trial of milk supplementation in pregnancy and childhood. SUBJECTS: A total of 951 individuals took part in a study of diet and growth in South Wales between 1972 and 1974 followed up from birth until their mid-20s. MEASUREMENTS: Anthopometric measures at birth, postnatally up to 5 years of age and in adulthood, and serum measures of IGF-I and IGF-I to IGFBP-3 ratio at mean age of 25 years. RESULTS: A total of 63 subjects (70%) provided blood for analysis. We found no association between birth dimensions and adult IGF-I. Subjects who exhibited 'catch-down growth' had lower IGF-I levels (P-value for trend 0.02). Adult height was positively related to IGF-I, for every one standard deviation increase in adult height, IGF-I increased by 3.75 ng/dl (95% CI 0.46-7.08, P = 0.03). Adiposity was inversely associated with the IGF-I and IGF-I to IGFBP-3 ratio and positively associated with IGFBP-3. The strength of the associations increased with age. Downward centile crossing at any time in childhood was associated with lower IGF-I whilst the highest levels were observed in subjects who were tall throughout their early life course. Adult height remained a significant predictor of IGF-I even after adjustment for earlier growth. CONCLUSIONS: Our results indicate that IGF-I levels in early adulthood are associated with patterns of childhood growth as well as adult stature and adiposity. These associations suggest the IGFs may contribute to anthropometric associations with cancer risk.

Adult↗

Associations of height, leg length, and lung function with cardiovascular risk factors in the Midspan Family Study.

BACKGROUND: Taller people and those with better lung function are at reduced risk of coronary heart disease (CHD). Biological mechanisms for these associations are not well understood, but both measures may be markers for early life exposures. Some studies have shown that leg length, an indicator of pre-pubertal nutritional status, is the component of height most strongly associated with CHD risk. Other studies show that height-CHD associations are greatly attenuated when lung function is controlled for. This study examines (1) the association of height and the components of height (leg length and trunk length) with CHD risk factors and (2) the relative strength of the association of height and forced expiratory volume in one second (FEV(1)) with risk factors for CHD. SUBJECTS AND METHODS: Cross sectional analysis of data collected at detailed cardiovascular screening examinations of 1040 men and 1298 women aged 30-59 whose parents were screened in 1972-76. Subjects come from 1477 families and are members of the Midspan Family Study. SETTING: The towns of Renfrew and Paisley in the West of Scotland. RESULTS: Taller subjects and those with better lung function had more favourable cardiovascular risk factor profiles, associations were strongest in relation to FEV(1). Higher FEV(1) was associated with lower blood pressure, cholesterol, glucose, fibrinogen, white blood cell count, and body mass index. Similar, but generally weaker, associations were seen with height. These associations were not attenuated in models controlling for parental height. Longer leg length, but not trunk length, was associated with lower systolic and diastolic blood pressure. Longer leg length was also associated with more favourable levels of cholesterol and body mass index than trunk length. CONCLUSIONS: These findings provide indirect evidence that measures of lung development and pre-pubertal growth act as biomarkers for childhood exposures that may modify an individual's risk of developing CHD. Genetic influences do not seem to underlie height-CHD associations.

Adult↗

Fruit, vegetables, and antioxidants in childhood and risk of adult cancer: the Boyd Orr cohort.

STUDY OBJECTIVE: To examine associations between food and nutrient intake, measured in childhood, and adult cancer in a cohort with over 60 years follow up. DESIGN AND SETTING: The study is based on the Boyd Orr cohort. Intake of fruit and vegetables, energy, vitamins C and E, carotene, and retinol was assessed from seven day household food inventories carried out during a study of family diet and health in 16 rural and urban areas of England and Scotland in 1937-39. PARTICIPANTS: 4999 men and women, from largely working class backgrounds, who had been children in the households participating in the pre-war survey. Analyses are based on 3878 traced subjects with full data on diet and social circumstances. MAIN RESULTS: Over the follow up period there were 483 incident malignant neoplasms. Increased childhood fruit intake was associated with reduced risk of incident cancer. In fully adjusted logistic regression models, odds ratios (95% confidence intervals) with increasing quartiles of fruit consumption were 1.0 (reference), 0.66 (0.48 to 0.90), 0.70 (0.51 to 0.97), 0.62 (0.43 to 0.90); p value for linear trend=0.02. The association was weaker for cancer mortality. There was no clear pattern of association between the other dietary factors and total cancer risk. CONCLUSIONS: Childhood fruit consumption may have a long term protective effect on cancer risk in adults. Further prospective studies, with individual measures of diet are required to further elucidate these relations.

Adult↗

Breast density: agreement of measures from film and digital image.

Mammographic density, in particular density from digital images, is increasingly used in breast cancer research. We investigated the concordance between density assigned by the same radiologist to a mammogram film and a digital image of the same mammogram. Two density measures were investigated, Wolfe parenchymal patterns and a six category classification (SCC) system of density. Included in the study were 78 women, 528 mammograms. Crude and weighted Kappa statistics were used to estimate agreement between the density assigned from the film and the image. Kappa for Wolfe measures was 71%, p<0.001 and for SCC measures was 54%, p<0.001. Weighted Kappa values were 79%, p<0.001 and 77%, p<0.001, respectively. There was some evidence to suggest that the digitized image may be assigned a higher Wolfe but not numerical category than the original film, and the magnitude of these differences was small. Neither age nor mammogram view (craniocaudal or mediolateral oblique) were related to the likelihood of agreement of the two density measurements. This evidence justifies the use of digital images in the visual assessment of breast density in research studies.

Breast Neoplasms↗

Gender differences in self-reported minor mental disorder and its association with suicide. A 20-year follow-up of the Renfrew and Paisley cohort.

BACKGROUND: Suicide rates are around three times higher in men than women; in contrast women have a higher prevalence of community-diagnosed depression. To investigate this paradox we examined the association of General Health Questionnaire (GHQ)-caseness (score > or = 4), a measure of possible minor mental disorder, with suicide risk in a general population cohort. METHODS: Data were derived from a cohort study based on the 8,466 men and women in the Renfrew and Paisley cohort who completed a 30-item GHQ in the period from 1972 to 1976 and who were followed up to 1995 for all-cause and suicide mortality. RESULTS: The long-term suicide risk associated with possible minor mental disorder was higher in men [hazard ratio 6.78 (1.36-33.71)] than women [hazard ratio 1.66 (0.43-6.45)]; test for interaction between gender and GHQ with respect to suicide risk: p = 0.09. CONCLUSION: These findings indicate either that the long-term risk of suicide in the context of a past episode of minor mental disorder is higher in males than females or that there are sex differences in the validity of responses to mental health screening questionnaires. Further research is required to replicate our finding in larger studies and, if confirmed, clarify which explanation underlies it.

Adolescent↗

Do patients who self-harm consult their general practitioner soon after hospital discharge? A cohort study.

BACKGROUND: Deliberate self-harm (DSH, attempted suicide) is one of the most common reasons for emergency hospital admission in Great Britain. Approximately 20 % of patients repeat self-harm in the 12 months after admission. The GP's role in DSH aftercare and the prevention of repeat episodes is unclear. METHODS: The data were obtained from a 12-month follow-up of a series of 968 consecutive patients from 49 practices who attended an accident and emergency (A&E) department in Bristol or Bath, UK, following an episode of self-harm between 26(th) May 1997 and 1(st) March 1999. RESULTS: Information on consultation patterns were available for 681 (70 %) of the patients. Two hundred and fourteen (31 %) of these consulted their GP in the week following the episode, 360 (53 %) within 4 weeks. Of the subjects, 44 % were discharged directly from A & E; these patients were more likely to consult their GP in the 4 weeks after the episode. Over the 12-month follow-up, 117 (17 %) attended hospital for a repeat episode of DSH; 9 % of these repeats occurred within 1 week and 28 % within 4 weeks of the index event. Although few (2 out of 11 patients--18 %) of those repeating in the first week after the index episode consulted their GP prior to repeating, 50 % (11/22) of those who repeated in the 1-4 weeks after an episode did so. CONCLUSIONS: Consultation patterns indicate that most people who deliberately self-harm consult their GP soon after the episode. This consultation may provide an opportunity for preventing repeat DSH and suicide.

Adolescent↗

Neurotic symptoms, stress, or deprivation: which is most closely associated with incidence of suicide? An ecological study of English Health Authorities.

BACKGROUND: Suicide rates, anxiety/depression scores and stress scores are routinely used as mental health indicators in populations, but their inter-relationships have not been explored. Our aim was to explore the association of suicide rates with anxiety/depression and stress scores, while also referring to deprivation scores, which are known to be linked to suicide rates. METHODS: We undertook an ecological analysis of English Health Authorities, regressing suicide rates (1993-1994), on General Health Questionnaire and stress scores (1994), and also on Jarman deprivation scores (1991). RESULTS: Overall, Jarman deprivation score was a better predictor of suicide rate than the psychological distress measures. There were no statistically significant associations between suicide rates and GHQ scores, although there was a weak association between suicide rate and mean stress level in women. CONCLUSIONS: Suicide rates, though important in themselves, are not reliable indicators of the levels of neurotic symptoms or stress in populations. Suicide rates are more strongly associated with area-based measures of social disadvantage, though a possible stress-suicide relationship in women could be investigated further.

Adolescent↗

Association between breast feeding and growth: the Boyd-Orr cohort study.

OBJECTIVE: To investigate the association of breast feeding with height and body mass index in childhood and adulthood. DESIGN: Historical cohort study, based on long term follow up of the Carnegie (Boyd-Orr) survey of diet and health in pre-war Britain (1937-1939). SETTING: Sixteen urban and rural districts in Britain. SUBJECTS: A total of 4999 children from 1352 families were surveyed in 1937-1939. Information on infant feeding and childhood anthropometry was available for 2995 subjects. MAIN OUTCOME MEASURES: Mean differences in childhood and adult anthropometry between breast and bottle fed subjects. RESULTS: Breast feeding was associated with the survey district, greater household income, and food expenditure, but not with number of children in the household, birth order, or social class. In childhood, breast fed subjects were significantly taller than bottle fed subjects after controlling for socioeconomic variables. The mean height difference among boys was 0.20 standard deviation (SD) (95% confidence interval (CI) 0.07 to 0.32), and among girls it was 0.14 SD (95% CI 0.02 to 0.27). Leg length, but not trunk length, was the component of height associated with breast feeding. In males, breast feeding was associated with greater adult height (difference: 0.34 SD, 95% CI 0.13 to 0.55); of the two components of height, leg length (0.26 SD, 95% CI 0.02 to 0.50) was more strongly related to breast feeding than trunk length (0.16 SD, 95% CI -0.04 to 0.35). Height and leg length differences were in the same direction but smaller among adult females. There was no association between breast feeding and body mass index in childhood or adulthood. CONCLUSIONS: Compared with bottle fed infants, infants breast fed in the 1920s and 1930s were taller in childhood and adulthood. As stature is associated with health and life expectancy, the possible long term impact of infant feeding on adult mortality patterns merits further investigation.

Adolescent↗

Population need for coronary revascularisation: are national targets for England credible?

OBJECTIVE: To estimate the need for coronary revascularisation, by using an incidence of indications approach, among 45-84 year olds with stable angina, unstable angina, and acute myocardial infarction. DESIGN: Modelling exercise. Six key steps along the pathway of care from initial diagnosis in primary or secondary care to revascularisation were defined and the frequency of indications estimated using routine data from hospital admissions and data from studies in the general population, and primary and secondary care. SETTING AND PATIENTS: Mid-1998 population of England. INTERVENTION: Coronary revascularisation. MAIN OUTCOME MEASURE: Ability to benefit (need), defined by randomised trials, expert panel ratings from the ACRE (appropriateness of coronary revascularisation) study, or by informal consensus. RESULTS: The need for coronary revascularisation was estimated to be 92 000 procedures, equivalent to a rate of 1861 per million population. Overall, the model of need exceeded current provision by 3.3:1, although among people aged 75 years and over the ratio was 7.7:1. A plausible upper estimate of need--obtained by assuming that 90% of patients with stable angina were referred from primary care and that angiography would be performed in 65% of patients with acute myocardial infarction and 75% of patients with unstable angina--was 2626 per million population. CONCLUSIONS: The national target of 1500 revascularisation procedures per million population is credibly related to population need, although upper estimates of need are considerably higher. Better understanding is required of the benefits of referring patients with specific indications from primary care. The greatest relative increase in provision is required for those aged 75 and older, among whom trial evidence of benefit is scant.

Aged↗

International trends in prostate-cancer mortality in the "PSA ERA".

Incidence and mortality from prostate cancer were rising in most countries until the late 1980s. Following a number of advances in the management of prostate cancer, including introduction of the prostate-specific antigen (PSA) test, there have been reports of declines in mortality in Canada, the United States and the United Kingdom. To investigate the extent to which this pattern was seen in other industrialised countries, we used routinely collected data to explore recent changes in prostate-cancer mortality. Trends in age-standardised death rates between 1979 and 1997 for men aged 50 to 79 years in 24 industrialised countries were compared using join point regression. Join point regression allows estimation of the annual percentage change in death rates and tests for significant changes in trend. During the period studied, age-standardised mortality increased at 1% to 2% per year in most countries. In 7 countries (Canada, United States, Austria, France, Germany, Italy and United Kingdom), a significant down-turn in age-standardised mortality was observed over the period 1988-1991. Trends in age-specific rates within these countries support a period effect on prostate-cancer mortality. Declines in mortality could result from any combination of either artefact, reduction in prostate-cancer incidence, a rise in competing causes of death or changes in the risk of death from prostate cancer. There are inconsistencies in the relationship between national mortality trends and uptake of PSA screening; further research is required to determine whether changes in death rates can be explained by international and secular variations in the treatment of prostate cancer.

Age Factors↗

Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study.

OBJECTIVE: To evaluate the effects on suicidal behaviour of legislation limiting the size of packs of paracetamol and salicylates sold over the counter. DESIGN: Before and after study. SETTING: UK population, with detailed monitoring of data from five liver units and seven general hospitals, between September 1996 and September 1999. SUBJECTS: People who died by suicidal or accidental overdose with paracetamol or salicylates or who died of undetermined causes; patients admitted to liver units with hepatic paracetamol poisoning; patients presenting to general hospitals with self poisoning after taking paracetamol or salicylates. MAIN OUTCOME MEASURES: Mortality from paracetamol or salicylate overdose; numbers of patients referred to liver units or listed for liver transplant; numbers of transplantations; numbers of overdoses and tablets taken; blood concentrations of the drugs; prothrombin times; sales to pharmacies and other outlets of paracetamol and salicylates. RESULTS: Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%) and the number from salicylates decreased by 48% (11% to 70%). Liver transplant rates after paracetamol poisoning decreased by 66% (55% to 74%). The rate of non-fatal self poisoning with paracetamol in any form decreased by 11% (5% to 16%), mainly because of a 15% (8% to 21%) reduction in overdoses of paracetamol in non-compound form. The average number of tablets taken in paracetamol overdoses decreased by 7% (0% to 12%), and the proportion involving >32 tablets decreased by 17% (4% to 28%). The average number of tablets taken in salicylate overdoses did not decrease, but 34% fewer (2% to 56%) salicylate overdoses involved >32 tablets. After the legislation mean blood concentrations of salicylates after overdose decreased, as did prothrombin times; mean blood concentrations of paracetamol did not change. CONCLUSION: Legislation restricting pack sizes of paracetamol and salicylates in the United Kingdom has had substantial beneficial effects on mortality and morbidity associated with self poisoning using these drugs.

Acetaminophen↗