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Biomedical subjects

D Gunnell

Publications and source records attributed to D Gunnell.

At least 19 recordsLinked to original sources

IGF1, growth pathway polymorphisms and schizophrenia: a pooling study.

It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2-3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia.

Bulgaria↗

IQ in early adulthood and later cancer risk: cohort study of one million Swedish men.

BACKGROUND: While several studies have reported an inverse relation between IQ and total mortality rates, little is known about the association, if any, between IQ and disease-specific outcomes, particularly cancer. METHODS: A cohort of 959,540 Swedish men who underwent IQ testing at military conscription at around 19 years of age, and who were followed for incident cancer. Hazards ratios for the relation between IQ and 20 cancer outcomes were computed using Cox regression. RESULTS: During an average of 19.5 years of follow-up, there were 10 273 new cancer cases. IQ showed few associations with the cancer end points studied. There was a suggestion that IQ was positively associated with lung cancer, and inversely related to stomach, oesophageal and liver malignancies, although effects were modest. The only robust gradient was found for IQ in relation to skin cancer (HRper one standard deviation advantage in IQ; 95% confidence interval 1.18; 1.13, 1.24; P value for trend across categories: <0.01), which was attenuated but retained statistical significance after adjustment for indices of socioeconomic position across the life course. CONCLUSIONS: In this large cohort of Swedish men followed into middle age, IQ was related to very few of the cancer outcomes under investigation. This indicates that the recent observation that low IQ is related to increased mortality rates may not be generated by an IQ-cancer gradient. Given that the present analyses are among the first to examine these associations, replication is required.

Adolescent↗

Identification of strategies to prevent death after pesticide self-poisoning using a Haddon matrix.

Despite pesticide self-poisoning causing around 300 000 deaths each year in the rural Asia Pacific region, no comprehensive public health response has yet been formulated. The authors have developed a Haddon matrix to identify factors that increase the risk of fatal rather than non-fatal pesticide self-poisoning in Sri Lanka. Many important host factors such as age, gender, and genetics are not alterable; factors that could be changed-alcohol use and mental health-have previously proved difficult to change. Interventions affecting agent or environmental factors may be easier to implement and more effective, in particular those limiting the human toxicity and accessibility of the pesticides, and the quality, affordability, and accessibility of health care in the community. Controlled studies are required to identify effective strategies for prevention and harm minimization and to garner political support for making the changes necessary to reduce this waste of life. Lessons learnt from Sri Lanka are likely to be highly relevant for much of rural Asia.

Alcohol Drinking↗

Association between sibship size and allergic diseases in the Glasgow Alumni Study.

BACKGROUND: Recent epidemiological studies consistently report an inverse association between sibship size and allergic disease, but evidence from individuals born before the 1980s is inconsistent. As information on relative permanence of this finding may offer clues to its biological explanation, the association between sibship size and allergic disease in individuals born between 1918 and 1952 was investigated. METHODS: Cross sectional surveys conducted by the Student Health Service at the University of Glasgow (1948-68) provided data on 14 140 men and women aged 16-30 years at the time of examination. The main outcome measures studied were self-reported asthma, eczema-urticaria, and hay fever. RESULTS: A total of 1677 individuals (11.9%) provided a positive history of at least one of the three allergic diseases: 457 (3.2%) asthma, 594 (4.2%) eczema-urticaria, and 885 (6.3%) hay fever. Compared with those without siblings (reference odds ratio = 1), the odds ratios (95% confidence intervals) for having any allergic disease among those with one, two or three siblings were 0.86 (0.75 to 0.99), 0.80 (0.69 to 0.93), and 0.70 (0.60 to 0.83), respectively (p(trend)<0.001). Increasing birth order and low socioeconomic position in childhood were associated with a lower risk of allergy. Adjustment for birth order, year of birth, age, sex, socioeconomic position in childhood, and family history of allergy did not materially alter the results. CONCLUSIONS: There is a robust inverse association between sibship size and allergic disease even among people born in the first half of the 20th century. These results favour relatively time-independent explanations for this phenomenon (such as the hygiene hypothesis or parity related changes in the intrauterine environment) over new environmental exposures.

Adolescent↗

Deaths from pesticide poisoning: a global response.

Self-poisoning with pesticides accounts for about a third of all suicides worldwide. To tackle this problem, the World Health Organization announced a global public health initiative in the second half of 2005. Planned approaches were to range from government regulatory action to the development of new treatments for pesticide poisoning. With broad-based support, this strategy should have a major impact on the global burden of suicide.

Global Health↗

The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women.

Previous investigations of the association of schizophrenia with patterns of pre- and post-natal growth have been based on small numbers of cases or have not taken account of the effects of prematurity on birthweight. We investigated the association of fetal growth with schizophrenia in a large cohort of Swedish males and females. We linked data from the Swedish Medical Birth Register (1973-1980), Inpatient and Discharge Register (1988-2002), Military Service Conscription Register (1990-1997), and the Population and Housing Censuses (1970 and 1990). Altogether 719,476 males and females were followed up from the age of 16 for a mean of 9.9 years. There were 736 incident cases of schizophrenia. Even in models that did not control for gestational age there was little evidence of an association between birthweight and schizophrenia (hazard ratio per kg increase in birthweight: 0.90 (95% CI 0.78 to 1.03); the hazard ratio in babies weighing <2.5 kg compared to 3.5-4.0 kg was 1.29 (95% CI 0.85 to 1.96). There was an inverse association of birth length with schizophrenia across the range of birth lengths. Short babies were at an increased risk (hazard ratio per 10 cm increase in birth length: 0.53, 95% CI 0.31 to 0.89 (fully adjusted model)). All associations were little changed when analyses were restricted to term (>36 week gestation) babies. In males, low body mass index and short height at age 18 were associated with increased risk. There is some evidence that patterns of risk in relation to fetal growth differ depending on post-natal growth patterns: the increased risk associated with low body mass index was restricted to long babies who became light adults. The exposures underlying these associations and the biological mechanisms mediating them require clarification.

Adolescent↗

Self-poisoning suicides in England: a multicentre study.

BACKGROUND: Suicide by self-poisoning is an important cause of death worldwide. A substantial proportion of those with a fatal outcome may come into contact with medical services before they die. AIM: To estimate the proportion of self-poisoning suicides who reached hospital alive; to compare those who reached hospital alive with those who did not; to describe in detail the clinical characteristics and medical management of those dying in hospital. DESIGN: Retrospective audit. METHODS: We studied 24 coroners' jurisdictions across England, reviewing coroners' files and identifying all suicides by self-poisoning (drugs and other ingestible poisons) from 1 January 2001 to 31 December 2001. RESULTS: Of the 214 individuals who completed suicide by self-poisoning during the study period, 49 (23%) reached hospital alive. Those reaching hospital were more likely to be female, more likely to have ingested paracetamol and less likely to have ingested co-proxamol. In the hospital sample, the commonest causes of death were respiratory (n = 10), hepatic or hepatorenal (n = 8), cardiac (n = 5), or a result of hypoxic brain injury (n = 5). Only 18% of in-hospital deaths occurred within 24 h of the overdose. DISCUSSION: Extrapolating to England as a whole, we might expect 300 self-poisoning suicides per year to reach hospital alive (6% of all suicides). Improved medical management might produce a small but significant reduction in the rate of suicide. Such interventions should not be restricted to the emergency care domain. Further research will help to clarify the likely contribution of improved medical management to suicide prevention.

Adult↗

Co-proxamol and suicide: preventing the continuing toll of overdose deaths.

Restricting means for suicide is a key element in suicide prevention strategies of all countries where these have been introduced. Preventing deaths from analgesic overdoses is highlighted in the National Suicide Prevention Strategy for England. The problem of self-poisoning with the prescription-only drug co-proxamol (dextropropoxyphene plus paracetamol) has received attention in several countries. We have conducted a review of the international literature related to possible strategies to tackle this problem. In England and Wales in 1997-1999, 18% of drug-related suicides involved co-proxamol; these constituted 5% of all suicides. Death usually results from the toxic effects of dextropropoxyphene on respiration or cardiac function. Death from co-proxamol overdose may occur rapidly, the lethal dose can be relatively low, and the effects are potentiated by alcohol and other CNS depressants. The majority of co-proxamol overdose deaths occur before hospital treatment can be received. The risk can extend to others in the household of the person for whom the drug is prescribed. While there is limited evidence that educational strategies have been effective in reducing deaths from co-proxamol poisoning, initiatives in Scandinavia, Australia and the UK to restrict availability of co-proxamol have produced promising results. Given the paucity of evidence for superior therapeutic efficacy of co-proxamol over other less toxic analgesics, there are good reasons to question whether it should continue to be prescribed.

Acetaminophen↗

A multicentre study of coproxamol poisoning suicides based on coroners' records in England.

AIMS: To examine in detail a series of coproxamol overdose deaths in order to provide information that will assist in the development of strategies to prevent such fatalities. METHOD: Inquest records in 24 coroners' jurisdictions in England on deaths between January 2000 and December 2001 which received a verdict of either suicide or undetermined cause (with a high or moderate probability of suicide) were examined. RESULTS: One hundred and twenty-three coproxamol poisoning suicides were identified. Alcohol was involved in 58.5% of the overdoses and these individuals generally had lower blood drug levels and consumed fewer tablets. Younger people were more likely to have consumed alcohol and to have lower levels of suicide intent. Nearly half the individuals had a history of self harm, and a third were under psychiatric care. The coproxamol had been prescribed for the individual in 81.5% of cases, although only in 55.0% of those aged 10-34 years. In other cases the source of the coproxamol was nearly always a family member or partner. Some deaths resulted from relatively small overdoses. CONCLUSIONS: Strategies to reduce self poisoning deaths due to coproxamol should take account of the high toxicity of coproxamol in overdose, especially when combined with alcohol, and the fact that risk of death extends beyond the person for whom the drug is prescribed.

Acetaminophen↗

Diet in childhood and adult cardiovascular and all cause mortality: the Boyd Orr cohort.

OBJECTIVE: To examine the association between childhood diet and cardiovascular mortality. DESIGN: Historical cohort study. SETTING: 16 centres in England and Scotland. PARTICIPANTS: 4028 people (from 1234 families) who took part in Boyd Orr's survey of family diet and health in Britain between 1937 and 1939 followed up through the National Health Service central register. EXPOSURES STUDIED: Childhood intake of fruit, vegetables, fish, oily fish, total fat, saturated fat, carotene, vitamin C, and vitamin E estimated from household dietary intake. MAIN OUTCOME MEASURES: Deaths from all causes and deaths attributed to coronary heart disease and stroke. RESULTS: Higher childhood intake of vegetables was associated with lower risk of stroke. After controlling for age, sex, energy intake, and a range of socioeconomic and other confounders the rate ratio between the highest and lowest quartiles of intake was 0.40 (95% confidence interval 0.19 to 0.83, p for trend 0.01). Higher intake of fish was associated with higher risk of stroke. The fully adjusted rate ratio between the highest and lowest quartile of fish intake was 2.01 (95% confidence interval 1.09 to 3.69, p for trend 0.01). Intake of any of the foods and constituents considered was not associated with coronary mortality. CONCLUSIONS: Aspects of childhood diet, but not antioxidant intake, may affect adult cardiovascular risk.

Adult↗

Studying suicide from the life course perspective: implications for prevention.

Suicide is an important contributor to premature mortality accounting for over 800 000 deaths worldwide every year. Environmental and genetic factors acting from before birth to old age affect an individual's risk of suicide. Risk is influenced not only by psychiatric illness and impulsive behaviour but also by factors such as the cultural acceptability of suicide, the ease of availability of lethal suicide methods, help-seeking behaviours in times of crisis and access to effective treatments following self-harm. Suicide prevention programmes might usefully focus on two discrete areas: the prevention of the psychiatric illnesses that precede suicide and tackling those risk factors particular to suicide such as media influences, help-seeking, the availability of methods and the medical management of self-harm.

Genetic Predisposition to Disease↗

Low intelligence test scores in 18 year old men and risk of suicide: cohort study.

OBJECTIVE: To examine the association between intelligence test scores in men, measured at age 18, and subsequent suicide. DESIGN: Record linkage study of the Swedish military service conscription register (1968-94) with the multi-generation register, cause of death register and census data. Four tests were performed at conscription covering logic, language, spatial, and technical skills. SETTING: Sweden. PARTICIPANTS: 987 308 Swedish men followed up for 5-26 years. MAIN OUTCOME MEASURE: Suicide. RESULTS: 2811 suicides occurred during follow up. The risk of suicide was two to three times higher in those with lowest compared with the highest test scores. The strongest associations were seen with the logic test: for each unit increase in test score the risk of suicide decreased by 12% (95% confidence interval 10% to 14%). Associations were only slightly attenuated when we controlled for parents' socioeconomic position. Greatest risks were seen among poorly performing offspring of well educated parents. CONCLUSIONS: Performance in intelligence tests is strongly related to subsequent risk of suicide in men. This may be due to the importance of cognitive ability in either the aetiology of serious mental disorder or an individual's capacity to solve problems while going through an acute life crisis or suffering from mental illness.

Educational Status↗

Dietary restraint and the mis-reporting of anthropometric measures by middle-aged adults.

OBJECTIVE: To assess whether levels of dietary restraint are associated with mis-reporting measures of adiposity by middle-aged adults. DESIGN: Cross-sectional study of middle-aged men and women, the parents of a group of young adults followed up since birth. METHODS: In all, 631 couples were mailed questionnaires and asked to record their height, weight and waist circumference. A paper tape measure with instructions for use was attached. Couples also completed the dietary restraint section of the Dutch Eating Behaviour Questionnaire, and provided information on employment and lifestyle habits. A subsample of participants was then invited to attend a clinic where detailed anthropometric measures were taken. RESULTS: In all, 435 women (69%) and 332 men (55%) completed the questionnaire; of those invited, 182 (85%) women and 102 (61%) men attended a clinic session. Regression analyses showed that the dietary restraint score was associated with the mis-reporting of BMI by women (P<0.01), but not men (test for interaction with gender, P=0.11). In women, the difference between the measured and reported BMI increased by 0.36 kg/m(2) (0.11-0.61) per unit increase in restraint score. This association was independent of age, smoking, social class, slimming, exercise frequency or television viewing time, but was attenuated in models controlling for measured BMI. The dietary restraint score was not associated with mis-reporting of waist circumference in men or women. CONCLUSIONS: Dietary restraint score may be a useful tool for identifying individuals more likely to mis-report anthropometric measurements, although associations may vary by gender.

Analysis of Variance↗

Is the season of birth association with psychosis due to seasonal variations in foetal growth or other related exposures? A cohort study.

OBJECTIVE: To investigate the association between season of birth and psychosis, and to assess whether any association is caused by seasonal fluctuations in foetal growth or other related exposures. METHOD: Cohort of 747 432 Swedish males and females born between 1973 and 1980 and followed up from 16 years of age to 31 December 1999. Psychiatric admissions were identified using the Swedish Inpatient Discharge Register. The analysis is based on the 696 025 subjects with complete data. RESULTS: A total of 506 (0.07%) subjects developed schizophrenia and 879 (0.13%) non-affective non-schizophrenic psychoses. There was a moderate increased risk of schizophrenia amongst winter births, hazard ratio 1.23 (95% confidence interval 0.96-1.59), but this did not reach conventional levels of statistical significance. There was no association with non-affective psychoses. We found no evidence that associations were confounded by measures of foetal growth or maternal socioeconomic position. There was no evidence that seasonal effects on schizophrenia differed in men and women. CONCLUSION: Season of birth associations with schizophrenia do not appear to be confounded by birth-related exposures.

Adolescent↗

Medical management of deliberate drug overdose: a neglected area for suicide prevention?

OBJECTIVES: Overdoses account for a quarter of all suicides in England. The number of people who survive the immediate effects of their overdose long enough to reach medical attention, but who subsequently die in hospital is unknown. The aim of this study was to determine the proportion of overdose suicides dying in hospital and describe their sociodemographic characteristics. METHOD: Cross sectional analysis of routinely collected Hospital Episode Statistics data for England (1997 to 1999) to identify hospital admissions for overdose among people aged 12+ and the outcome of these admissions. RESULTS: Between 1997 and 1999 there were 233 756 hospital admissions for overdose, 1149 (0.5%) of these ended in the death of the patient such deaths accounted for 28% [corrected] of all overdose suicides and 8% [corrected] of total suicides. The median time between admission and death was three days (interquartile range one to nine days). The most commonly identified drugs taken in fatal overdose were paracetamol compounds, benzodiazepines, and tricyclic/tetracyclic antidepressants. CONCLUSION: Around a quarter of all overdose suicide deaths occur subsequent to hospital admission. Further more detailed research is required to discover if better pre-admission and in-hospital medical management of those taking serious overdoses may prevent some of these deaths.

Acetaminophen↗

Associations of components of adult height with coronary heart disease in postmenopausal women: the British women's heart and health study.

OBJECTIVE: To assess the associations between components of adult height and coronary heart disease (CHD) in postmenopausal women. METHODS: Cross sectional analysis of 4286 women randomly selected from 23 British towns. The association of components of adult height with prevalent CHD (n = 694) were assessed. RESULTS: Shorter stature, shorter leg length, and trunk length were all associated with CHD in age adjusted analyses. The association between trunk length and CHD was attenuated to the null with adjustment for smoking. The leg length-CHD association was independent of smoking, socioeconomic position in childhood and adulthood, birth weight, and other potential confounders. Insulin resistance did not appear to be an important mediating factor in the association between leg length and CHD. After full adjustment for all potential confounding factors the odds ratio (95% confidence interval) of CHD for a 1 SD (4.3 cm) increase in leg length was 0.84 (0.77 to 0.93) and the odds ratio for a 1 SD (0.05) increase in the leg to trunk ratio was 0.85 (0.79 to 0.95). CONCLUSIONS: The specific association between leg length and CHD suggests that early life environmental exposures that influence skeletal growth also influence CHD risk in later life.

Aged↗