Showing papers by "George Davey Smith published in 2001"

Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis.

Abstract: This is the second in a series of four articles Studies that show a significant effect of treatment are more likely to be published, be published in English, be cited by other authors, and produce multiple publications than other studies.1–8 Such studies are therefore also more likely to be identified and included in systematic reviews, which may introduce bias.9 Low methodological quality of studies included in a systematic review is another important source of bias.10 All these biases are more likely to affect small studies than large ones. The smaller a study the larger the treatment effect necessary for the results to be significant. The greater investment of time and money in larger studies means that they are more likely to be of high methodological quality and published even if their results are negative. Bias in a systematic review may therefore become evident through an association between the size of the treatment effect and study size—such associations may be examined both graphically and statistically. #### Summary points Asymmetrical funnel plots may indicate publication bias or be due to exaggeration of treatment effects in small studies of low quality Bias is not the only explanation for funnel plot asymmetry; funnel plots should be seen as a means of examining “small study effects” (the tendency for the smaller studies in a meta-analysis to show larger treatment effects) rather than a tool for diagnosing specific types of bias Statistical methods may be used to examine the evidence for bias and to examine the robustness of the conclusions of the meta-analysis in sensitivity analyses “Correction” of treatment effect estimates for bias should be avoided as such corrections may depend heavily on the assumptions made Multivariable models may be used, with caution, to examine the relative importance of different types of bias ### Funnel plots Funnel …

Sifting the evidence—what's wrong with significance tests?

Abstract: The findings of medical research are often met with considerable scepticism, even when they have apparently come from studies with sound methodologies that have been subjected to appropriate statistical analysis. This is perhaps particularly the case with respect to epidemiological findings that suggest that some aspect of everyday life is bad for people. Indeed, one recent popular history, the medical journalist James Le Fanu's The Rise and Fall of Modern Medicine , went so far as to suggest that the solution to medicine's ills would be the closure of all departments of epidemiology.1 One contributory factor is that the medical literature shows a strong tendency to accentuate the positive; positive outcomes are more likely to be reported than null results.2–4 By this means alone a host of purely chance findings will be published, as by conventional reasoning examining 20 associations will produce one result that is “significant at P=0.05” by chance alone. If only positive findings are published then they may be mistakenly considered to be of importance rather than being the necessary chance results produced by the application of criteria for meaningfulness based on statistical significance. As many studies contain long questionnaires collecting information on hundreds of variables, and measure a wide range of potential outcomes, several false positive findings are virtually guaranteed. The high volume and often contradictory nature5 of medical research findings, however, is not only because of publication bias. A more fundamental problem is the widespread misunderstanding of the nature of statistical significance. #### Summary points P values, or significance levels, measure the strength of the evidence against the null hypothesis; the smaller the P value, the stronger the evidence against the null hypothesis An arbitrary division of results, into “significant” or “non-significant” according to the P value, was not the intention of the …

Height, Leg Length, and Cancer Risk: A Systematic Review

Abstract: Associations between height and cancer risk have been reported in a number of prospective studies (1, 2). Taller individuals appear to be at increased risk. Furthermore, ecologic analyses indicate that geographic patterns of cancer incidence and mortality are associated with variations in population height (3-5). The most consistent associations have been found in relation to breast cancer (6-8), although associations have also been reported for many other cancer sites. Therefore, common mechanisms may underlie these associations, but their precise nature remains unclear. Models of cancer pathogenesis suggest that cancer arises as a result of DNA damage at a number of specific loci important in the regulation of the cell cycle or DNA repair (9, 10). While specific oncogenes, tumor suppresser genes, and cancer susceptibility genes have been identified, it has become increasingly apparent that epigenetic pathways also underlie the development of some malignancies. Several mechanisms may be common to many different cancers. For example, angiogenesis (the formation of new blood vessels) is an absolute requirement for the growth of all solid tumors (11). Similarly, apoptosis is a mechanism for eliminating damaged or dangerous cells from the body, and thus it provides a natural defense against cancer. The most potent cell survival factor controlling apoptosis is insulin-like growth factor I (IGF-I). Raised levels of IGF-I and reduced levels of its main binding protein, insulin-like growth factor (IGF)- binding protein 3, may diminish this defense against a range of cancers. In support of this notion, recent prospective research has demonstrated that raised levels of IGF-I are associated with increased risks of prostate (12-14), breast (15), and colorectal (16, 17) cancers.

Dietary fat intake and prevention of cardiovascular disease: systematic review.

Abstract: Objective To assess the effect of reduction or modification of dietary fat intake on total and cardiovascular mortality and cardiovascular morbidity. Design Systematic review. Data sources Cochrane Library, Medline, Embase, CAB abstracts, SIGLE, CVRCT registry, and biographies were searched; trials known to experts were included. Included studies Randomised controlled trials stating intention to reduce or modify fat or cholesterol intake in healthy adult participants over at least six months. Inclusion decisions, validity, and data extraction were duplicated. Meta›analysis (random effects methodology), meta›regression, and funnel plots were performed. Results 27 studies (30 902 person years of observation) were included. Alteration of dietary fat intake had small effects on total mortality (rate ratio 0.98; 95% confidence interval 0.86 to 1.12). Cardiovascular mortality was reduced by 9% (0.91; 0.77 to 1.07) and cardiovascular events by 16% (0.84; 0.72 to 0.99), which was attenuated (0.86; 0.72 to 1.03) in a sensitivity analysis that excluded a trial using oily fish. Trials with at least two years’ follow up provided stronger evidence of protection from cardiovascular events (0.76; 0.65 to 0.90). Conclusions There is a small but potentially important reduction in cardiovascular risk with reduction or modification of dietary fat intake, seen particularly in trials of longer duration.

Multiple hit read-out of a microchannel plate detector with a three-layer delay-line anode

Abstract: We have developed a delay-line read-out technique for microchannel plate detectors with an increased acceptance for multiple hit events compared to standard two-layer delay-line anodes. This technique allows unambiguous determination of arrival time and position of at least four simultaneously detected particles, and/or to detect an even larger number of particles in a shower, as long as any two particles do not arrive both at the same time and at the same position within certain limits. We demonstrate and discuss the abilities and limitations of this technique and the relevance for certain experimental tasks.

Blood pressure reactions to acute psychological stress and future blood pressure status: a 10-year follow-up of men in the Whitehall II study.

Abstract: Objective The aim of this study was to examine whether blood pressure reactions to mental stress predicted future blood pressure and hypertension. Methods Blood pressure was recorded at an initial medical screening examination after which blood pressure reactions to a mental stress task were determined. A follow-up screening assessment of blood pressure and antihypertensive medication status was undertaken 10 years later. Data were available for 796 male public servants, between 35 and 55 years of age upon entry to the study. Results Systolic blood pressure reactions to mental stress were positively correlated with follow-up screening systolic blood pressure and to a lesser extent, follow-up diastolic pressure. In multivariate tests, by far the strongest predictors of follow-up blood pressures were initial screening blood pressures. In the case of follow-up systolic blood pressure, systolic reactions to stress emerged as an additional predictor of follow-up systolic blood pressure. With regard to follow-up diastolic blood pressure, reactivity did not enter the analogous equations. The same outcomes emerged when the analyses were adjusted for medication status. When hypertension at 10-year follow-up was the focus, both systolic and diastolic reactions to stress were predictive. However, with correction for age and initial screening blood pressure, these associations were no longer statistically significant. Conclusions The results of this study provide modest support for the hypothesis that heightened blood pressure reactions to mental stress contribute to the development of high blood pressure. At the same time, they question the clinical utility of stress testing as a prognostic device.

Uses and abuses of meta-analysis.

Abstract: Meta-analysis, the statistical combi- nation of results from several studies to produce a single estimate of the effect of a treatment, continues to attract controversy. We illustrate the potentials and pitfalls of meta-analysis of controlled clinical trials. Cumulative meta-analysis demonstrates that this technique could prevent delays in the introduction of effective treatments. Meta-analyses are, however, liable to numerous biases both at the level of the individual trial (' garbage in, garbage out') and the dissemination of trial results (publication bias). We argue that meta-analysis should be performed only within the framework of systematic reviews - that is, reviews prepared using a systematic approach to minimise bias and address the combinability of studies.

Sifting the evidence—what's wrong with significance tests?

Abstract: The findings of medical research are often met with considerable scepticism, even when they have apparently come from studies with sound methodologies that have been subjected to appropriate statistical analysis. This is perhaps particularly the case with respect to epidemiological findings that suggest that some aspect of everyday life is bad for people. Indeed, one recent popular history, the medical journalist James Le Fanu's The Rise and Fall of Modern Medicine , went so far as to suggest that the solution to medicine's ills would be the closure of all departments of epidemiology.1 One contributory factor is that the medical literature shows a strong tendency to accentuate the positive; positive outcomes are more likely to be reported than null results.2–4 By this means alone a host of purely chance findings will be published, as by conventional reasoning examining 20 associations will produce one result that is “significant at P = 0.05” by chance alone. If only positive findings are published then they may be mistakenly considered to be of importance rather than being the necessary chance results produced by the application of criteria for meaningfulness based on statistical significance. As many studies contain long questionnaires collecting information on hundreds of variables, and measure a wide range of potential outcomes, several false positive findings are virtually guaranteed. The high volume and often contradictory nature5 of medical research findings, however, is not only because of publication bias. A more fundamental problem is the widespread misunderstanding of the nature of statistical significance. In this paper we consider how the practice of significance testing emerged; an arbitrary division of results as “significant” or “non-significant” (according to the commonly used threshold of P = 0.05) was not the intention of the founders of statistical inference. P values need to be …

Exporting failure? Coronary heart disease and stroke in developing countries

Abstract: The burden of coronary heart disease (CHD) and stroke is considerable, representing 30% of all deaths worldwide, that is about 15 million deaths a year, of which 11 million are in developing or transitional countries.1 Commentators have predicted a global epidemic of cardiovascular disease on the basis of current trends.2 One enthusiast has even stated that ‘In fact, cardiovascular disease is already the leading cause of death not only in developed countries but, as of the mid-1990s, in developing countries as well’,3 a statement not supported by data in the World Health Report 2000.4 Citing statistics in this way undoubtedly fuels the view that ‘something must be done’, promulgated by bodies such as the World Heart Federation.1 Clearly the absolute numbers of deaths should be related to the population at risk, which is substantially greater in developing countries of the world. The Global Burden of Disease study has attempted to provide a picture derived not only from mortality data but also from cardiovascular disability, some of which is consequent upon diseases other than coronary heart disease and stroke.5 This study demonstrated that while ischaemic heart disease and stroke were 5th and 6th in the 1990 league table of disability adjusted life years (DALYs), they contributed 20.4% of the DALYs in developed countries, but only 8.3% in developing countries.6 Concerns about the accuracy of international mortality data and the virtual absence of relevant incidence and disability data clearly need to be addressed urgently if the approach is to have validity.7 Epidemiological studies in developing countries, although small in number, provide evidence that stroke mortality rates tend to be higher than coronary heart disease rates,8 and may be considerably higher than in developed countries,9 but both stroke prevalence10 and coronary heart disease prevalence11 are considerably lower, which may reflect more severe disease or worse health services, leading to higher case-fatality rates. The World Health Organization MONICA surveys, while dominated by developed countries, have data from China which experienced the lowest coronary heart disease event rates of any MONICA centre, but one of the highest annual relative increases among men, but not women.12 Adverse risk factor changes in Chinese men, but not women, were associated with the increased male event rate.13 Surveys of cardiovascular risk factors in developing countries tend to show lower mean levels of blood cholesterol, blood pressure and body mass index; although urban levels may be closer to those found in developed countries.10,14,15 Smoking in developing countries is of growing concern as consumption in the developed world tends to contract, but manufacturers’ cigarette production and profits increase markedly.16 Of the 1.1 billion smokers worldwide, 800 million live in developing countries—with 300 million in China. It is to be expected that the cardiovascular disease consequences of smoking will be increasingly felt as these comparatively young smokers age.17 It has been estimated that current smoking uptake rates in China will result in 100 million deaths among the 0.3 billion men aged now under 30 years, with half of these deaths occurring in middle age.18

Job insecurity in white-collar workers: toward an explanation of associations with health.

Abstract: This article describes 2 studies that examined changes in psychosocial work characteristics (job strain model) and health-related behaviors as potential explanations of the job insecurity-health relationship in a longitudinal cohort of white-collar British civil servants. Job insecurity arising from anticipation of change was associated with a modest increase in self-reported morbidity, whereas chronic job insecurity was associated with some adverse physiological changes. Anticipation of change and chronic job insecurity were associated with adverse changes in other psychosocial work characteristics, but few changes were significant and consistent across both exposure groups. Changes in health-related behaviors associated with either exposure were slight. Apart from a minor role for social support at work in both sexes and a modest role for job demands in women, adverse changes in these factors explain little of the job insecurity-health relationship.

Employment status and health after privatisation in white collar civil servants: prospective cohort study.

Abstract: Objectives: To determine whether employment status after job loss due to privatisation influences health and use of health services and whether financial strain, psychosocial measures, or health related behaviours can explain any findings Design: Data collected before and 18 months after privatisation Setting: One department of the civil service that was sold to the private sector Participants: 666 employees during baseline screening in the department to be privatised Main outcome measures: Health and health service outcomes associated with insecure re-employment, permanent exit from paid employment, and unemployment after privatisation compared with outcomes associated with secure re-employment Results: Insecure re-employment and unemployment were associated with relative increases in minor psychiatric morbidity (mean difference 156 (95% confidence intervals interval 10 to 22) and 125 (06 to 20) respectively) and having four or more consultations with a general practitioner in the past year (odds ratio 204 (11 to 38) and 239 (12 to 47) respectively) Health outcomes for respondents permanently out of paid employment closely resembled those in secure re-employment, except for a substantial relative increase in longstanding illness (225; 11 to 44) Financial strain and change in psychosocial measures and health related behaviours accounted for little of the observed associations Adjustment for change in minor psychiatric morbidity attenuated the association between insecure re-employment or unemployment and general practitioner consultations by 26% and 27%, respectively Conclusions: Insecure re-employment and unemployment after privatisation result in increases in minor psychiatric morbidity and consultations with a general practitioner, which are possibly due to the increased minor psychiatric morbidity

Perceived stress and coronary heart disease risk factors: the contribution of socio-economic position.

Abstract: Objectives. The aim of this study was to explore the relationship between risk factors for coronary heart disease (CHD) and perceived stress, adjusted for socio-economic position. Design. Cross-sectional analysis of CHD risk factors, perceived stress and socio-economic position. Method. A cohort of employed Scottish men (N = 5848) and women (N = 984) completed a questionnaire and attended a physical examination. Results. Higher socio-economic groups registered higher perceived stress scores. Perceived stress was associated with the following CHD risk factors in the expected direction: high plasma cholesterol, little recreational exercise, cigarette smoking, and high alcohol consumption. Contrary to expectations, stress was related negatively to high diastolic blood pressure, body mass index (BMI) and low forced expiratory volume. Correction for socio-economic position tended to abolish the associations between stress and physiological risk factors; the associations between stress and behavioural risk factors withstood such correction. The residual patterns of associations between perceived stress and CHD risk were broadly similar for men and women. A lower BMI, a greater number of cigarettes smoked, and greater alcohol consumption were associated with higher levels of perceived stress for both sexes. Lower levels of recreational exercise were associated with higher levels of stress for men only. Conclusions. Self-reported stress is related to health-related behaviours and to physiological CHD risk factors. The direction of the association with physiological risk was often contrary to expectation and appeared to be largely due to confounding by socio-economic position. In contrast, the association with health-related behaviours was in the expected direction and was largely independent of such confounding.

Thermal stability of electrodeposited nanocrystalline nickel and iron - nickel alloys

Abstract: The thermal stability of electrodeposited nanocrystalline nickel and iron–nickel alloys has been studied using TEM, X-ray diffraction, and atom probe analysis. All of the as deposited materials were purely fcc and had grain sizes of 10–20 nm. Heat treatment of nanocrystalline nickel in the range 190–320°C resulted in abnormal grain growth with an activation energy of 122±15 kJ mol-1. Abnormal grain growth in Fe–50 at.-%Ni was only observed at 400°C but not at 220 or 300°C, where grain growth was very slow. In Fe–33 at.-%Ni, room temperature aging resulted in the formation of large grained areas (∼1 µm), some of which transformed to bcc. In heat treated nickel specimens, some evidence of sulphur and carbon enrichment was found at grain boundaries.

Social class differences in lung cancer mortality: risk factor explanations using two Scottish cohort studies

Abstract: Background The study investigated differences in lung cancer mortality risk between social classes. Methods Twenty years of mortality follow-up were analysed in 7052 men and 8354 women from the Renfrew/Paisley general population study and 4021 working men from the Collaborative study. Results More manual than non-manual men and women smoked, reported morning phlegm, had worse lung function and lived in more deprived areas. Lung cancer mortality rates were higher in manual than non-manual men and women. Significantly higher lung cancer mortality risks were seen for manual compared to non-manual workers when adjusting for age only and adjustment for smoking reduced these risks to 1.41 (95% CI : 1.12-1.77) for men in the Renfrew/Paisley study, 1.28 (95% CI : 0.94-1.75) for women in the Renfrew/Paisley study and 1.43 (95% CI: 1.02-2.01) for men in the Collaborative study. Adjustment for lung function, phlegm and deprivation category attenuated the risks which were of borderline significance for men in the Renfrew/Paisley study and non significant for women in the Renfrew/Paisley study and men in the Collaborative study. Adding extra socioeconomic variables, available in the Collaborative study only, reduced the difference between the manual and non-manual social classes completely. Conclusions There is a difference in lung cancer risk between social classes, in addition to the effect of smoking. This can be explained by poor lung health, deprivation and poor socioeconomic conditions throughout life. As well as anti-smoking measures, reducing socioeconomic inequalities and targeting individuals with poor lung function for help with smoking cessation could help reduce future lung cancer incidence and mortality.

Optimization of mechanical properties of high-carbon pearlitic steels with Si and V additions

Abstract: Systematic research has been undertaken on the effects of single and combined additions of vanadium and silicon on the mechanical properties of pearlitic steels being developed for wire rod production. Mechanical test results demonstrate that the alloy additions are beneficial to the mechanical properties of the steels, especially the tensile strength. Silicon strengthens pearlite mainly by solid-solution strengthening of the ferrite phase. Vanadium increases the strength of pearlite mainly by precipitation strengthening of the pearlitic ferrite. When added separately, these elements produce relatively greater strengthening at higher transformation temperatures. When added in combination the behavior is different, and substantial strength increments are produced at all transformation temperatures studied (550 °C to 650 °C). The addition of silicon and vanadium to very-high-carbon steels (>0.8 wt pct C) also suppresses the formation of a network of continuous grain-boundary cementite, so that these hypereutectoid materials have high strength coupled with adequate ductility for cold drawing. A wire-drawing trial showed that total drawing reductions in area of 90 pct could be obtained, leading to final tensile strengths of up to 2540 MPa in 3.3-mm-diameter wires.

Socio-economic position and coronary heart disease risk factors in youth - Findings from the Young Hearts Project in Northern Ireland

Abstract: Background: This study investigates the existence of socioeconomic differentials in behavioural and biological risk factors for coronary heart disease in young people from Northern Ireland, taking into account differences in biological maturation. Methods: A school-based prospective study, with measurements in 1989/1990 and 1992/1993. Socio-economic position was based on occupational level of the main family breadwinner. Behavioural risk factors included were physical inactivity, the intake of total energy, dietary fat and a number of mlcronutrients. Biological risk factors included were blood pressure, body fatness, llpoproteins and cardio-pulmonary fitness. Biological maturation was based on Tanner's stages. Participants: 251 boys and 258 girls who were measured at the age of 12 years and re-examined at the age of 15 years. Results: Cross-sectional analyses showed that socio-economic differences in cholesterol intake (In boys) and physical inactivity and total energy intake (in girls) were present at 12 and 15 years of age, while differences in fat and fruit intake and smoking behaviour (in boys and girls) became established at the age of 15 years, with unfavourable levels in subjects in the manual group. Longitudinal analyses confirmed that differences in behavioural risk factors exist or develop during adolescence. No clear pattern of differences in biological risk factors was found by socio-economic position. Adjustment for biological maturation did not materially alter the results. Conclusion: Differences in lifestyle by socio-economi c position seem to become established in adolescence. These differences however, are not (yet) reflected in differences in biological risk factors by socio-economic position.

Physical activity and cause-specific mortality in men: further evidence from the Whitehall study.

Abstract: Reports of studies relating physical activity to stroke and cancer sub-types indicate inconsistent findings. Some are hampered by low statistical power, owing to a low number of events, and a failure to adjust for potential confounding variables. The purpose of this study was to relate physical activity to 12 mortality endpoints in a prospective cohort study of 11,663 men aged 40-64 years who responded to an enquiry about travel activity during a baseline medical examination conducted between 1967 and 1969. During 25 years of follow-up there were 4672 deaths. Travel activity was inversely related to mortality attributable to all-causes, coronary heart disease, respiratory disease and lung cancer, whereas the association with stroke was positive. There was evidence for attenuation of some of these associations on adjustment for potentially confounding variables. Our simplistic measure of physical activity may, in part, explain the weak associations seen.

Poverty, inequality and health in Britain : 1800-2000 : a reader

Abstract: Introduction Further reading Timeline Extracts from: Thomas Clarkson's An essay on the impolicy of the African slave trade (1788) and An essay on the slavery and commerce of the human species, particularly the African (1785, 1817) Thomas Malthus' An essay on the principle of population (1798, 1985) Factory Inquiry Commission Report (1833) William Farr's Vital statistics - A memorial volume (1837, 1885, 1975) Edwin Chadwick's Report on the sanitary conditions of the labouring population of Gt Britain (1842, 1965) Friedrich Engels' The condition of the working class in England (1845, 1987) Henry Mayhew's London labour and the London poor (1851-52) Karl Marx's Inaugural address of the International Working Men's Association (1864, 1992) Benjamin Seebohm Rowntree's Poverty: A study of town life (1901, 1971) Charles Booth's On the city: Physical pattern and social structure (1902-3, 1967) Maud Pember Reeves' Round about a pound a week (1913, 1988) Robert Tressell 's The ragged trousered philanthropists (1914, 1955) Edgar L. Collis and Major Greenwood's The health of the industrial worker (1921) Frank W. White's 'Natural and social selection: a "Blue-Book" analysis' (1928) George C.M. M'Gonigle and J. Kirby's Poverty and public health (1936) John Boyd Orr's Food, health and income (1936, 1937) Wal Hannington's The problem of distressed areas (1937) Margery Spring Rice's Working-class wives: Their health and conditions (1939) William Beveridge's Social Insurance and Allied Services (1942) Richard Titmuss' Birth, poverty and wealth (1943) J.N. Morris' Health (1944) John Hewetson's Ill-health, poverty and the state (1946) Aneurin Bevan's In place of fear (1947) Brian Abel-Smith and Peter Townsend's The poor and the poorest (1965) Robert Roberts' The classic slum: Salford life in the first quarter of the century (1971) Julian Tudor Hart's 'The inverse care law' (1971) Inequalities in health: Report of a Research Working Group chaired by Sir Douglas Black (The Black Report) (1980) Independent Inquiry into Inequalities in Health (The Acheson Report) (1998).

Are women more sensitive to smoking than men? Findings from the Renfrew and Paisley study.

Abstract: Background Prescott et al. found that the relative risks associated with smoking for respiratory and vascular deaths were higher for women who inhale than for inhaling men, and found no gender differences in relative risks of smoking-related cancers. The purpose of the present study was to assess whether these findings are reproducible, using data from the Renfrew and Paisley study. Methods Age-standardized mortality rate differences and age-adjusted mortality rate ratios (using Cox’s proportional hazard model) were calculated for male and female smokers by amount smoked compared with never smokers. These analyses were repeated after excluding non-inhalers. Results The all-cause mortality rate ratio was higher for men than for women in all categories of amount smoked, although this difference was only statistically significant in the light smokers (1.83 [95% CI : 1.61‐2.07] for men and 1.41 [95% CI : 1.28‐1.56] for women, P = 0.001). The cause-specific mortality rate ratios tended to be higher for men than for women, and this difference was most substantial for neoplasms (2.57 [95% CI : 2.01‐3.29] for male light smokers and 1.35 [95% CI : 1.14‐1.61] for female light smokers, P , 0.001) and, in particular, for lung cancer (11.10 [95% CI : 5.89‐20.92] for male light smokers and 4.73 [95% CI : 2.99‐7.50] for female light smokers, P = 0.03). Furthermore, looking at the rate differences the effects of smoking were uniformly greater in men than in women. These results were virtually unchanged after excluding non-inhalers. Conclusion We found similar results to Prescott et al. when all smokers were considered, but could not reproduce their findings when non-inhalers were excluded. Given the fact that we showed greater rate differences in men than in women, we think that it is too early to conclude that women may be more sensitive than men to some of the deleterious effects of smoking.

Changes in blood pressure among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys.

Abstract: Objectives: To examine the changes in blood pressure over time in a cohort of young adults attending university between 1948 and 1968. Design: Cross sectional study. Setting: Glasgow University. Participants: 12 414 students aged 16-25 years—9248 men (mean age 19.9 years) and 3164 women (19.2 years)—who participated in health screening on entering university between 1948 and 1968. Main outcome measures: Systolic and diastolic blood pressure. Results: In male students mean systolic blood pressure adjusted for age decreased from 134.5 (95% confidence interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to 126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from 80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) mm Hg. For female students the corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to 121.4) mm Hg and from 79.7 (78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg. Adjustment for potential confounding factors made little difference to these findings. The proportion of students with hypertension declined substantially in both sexes. Conclusions: Substantial declines in systolic and diastolic blood pressure over time were occurring up to 50 years ago in young adults who were not taking antihypertensive medication. Since blood pressure tracks into adult life, the results of the cross sectional comparisons suggest that factors acting in early life may be important in determining population risk of cardiovascular disease. Changes in such factors may have made important contributions to the decline in rates of cardiovascular diseases, particularly stroke, seen in developed countries during the past century. What is already known on this topic Mortality from stroke in developed countries decreased throughout the 20th century; declines in mortality from coronary heart disease occurred more recently Explanations may include favourable trends in risk factors, including blood pressure Since blood pressure tracks into adulthood, description of the trends occurring in blood pressure in young adults may help to elucidate the critical periods involved in influencing trends in blood pressure What this study adds Declines in blood pressure over time were taking place up to 50 years ago in young adults These changes did not result from use of antihypertensive medications and point to the importance of factors in early life in determining blood pressure and risk of subsequent cardiovascular disease

How much does place matter

Abstract: Anecdote is the singular of data Danny Dorling Do we care about area effects? George Smith, Michael Noble, Gemma Wright Evidence-based policy and practice Roger Burrows, Jonathan Bradshaw Is there a place for area-based initiatives? Heather Joshi On reinvented wheels Charles Pattie Multilevel modeling might not be the answer Richard Mitchell Unemployment, nonemployment, and labour-market disadvantage Anne E Green Reply: Ward-level deprivation and individual social and economic outcomes in the British Household Panel Study Andrew McCulloch

Are Two Really Better Than One? Empirical Examination of Repeat Blood Pressure Measurements and Stroke Risk in the Renfrew/Paisley and Collaborative Studies

Abstract: Background and Purpose — Blood pressure measured on 2 occasions in 2 large prospective cohort studies in Scotland was related to stroke, defined as stroke mortality or hospital admission for stroke. The purpose was to investigate whether 2 blood pressure readings gave a more accurate estimate of stroke risk over a long follow-up period than 1 reading. Methods — In the 1970s, the Renfrew/Paisley general population study investigated 3060 men and 3502 women and the Collaborative study investigated 2683 employed men on 2 occasions. The mean years between screening were 4 and 5, respectively. Blood pressure measured on the 2 occasions was related to stroke risk in 17-year and 21-year follow-up periods after the second screening, respectively. Results — For both systolic and diastolic blood pressure, the mean of the measures on the 2 occasions, the maximum of the 2 measures and the measure corrected for regression dilution was more strongly related to stroke over the follow-up periods than either single measure. Conclusions — Two blood pressure measurements seem better than 1 for indicating stroke risk. Underestimation using single measures will lead to both misclassification of the risk of disease for individuals and also the population-attributable risk of disease associated with elevated blood pressure.

Characterisation and comparison of novel ligands for the nociceptin/orphanin FQ receptor.

Abstract: Studies of nociceptin/orphanin FQ (NC) have been hampered by the paucity of available ligands with activity at the nociceptin receptor (NCR). In this study we have compared the agonist profile of NC and a novel NCR agonist, Ro65-6570, in a series of radioligand binding studies and effects on forskolin-stimulated cAMP formation in Chinese hamster ovary (CHO) cells expressing the recombinant human NCR (CHOhNCR). In addition, we report the effects of three antagonists, [Nphe1]NC(1–13)NH2, J-113397 and III-BTD, on these responses. In radioligand binding studies Ro65-6570, [Nphe1]NC(1–13)NH2, J-113397 and III-BTD displaced [3H]NC with similar pK i values (8.4–8.8). This compares with a pK D of 10.2 for NC in a direct saturation experiment. [Nphe1]NC(1–13)NH2 and J-113397 showed at least 100-fold selectivity over classical opioid receptors. Both NC and Ro65-6570 produced a concentration-dependent inhibition of cAMP formation with pEC50 values of 9.56±0.06 and 8.68±0.04, respectively. Maximum inhibition achieved was 100%. [Nphe1]NC(1–13)NH2, J-113397 and III-BTD produced a parallel rightward shift in the concentration-response curves to both NC and Ro65-6570 with pK B values of ~6.5, ~7.5 and ~7.7, respectively. Importantly, all three antagonists were devoid of residual agonist activity. Collectively, these data indicate the value of Ro65-6570, [Nphe1]NC(1–13)NH2, J-113397 and III-BTD in studies of the physiological role played by NC. However, due to the relatively poor selectivity of Ro65-6570 and III-BTD caution should be exercised when using tissues that co-express µ-opioid receptors.

Effect of a COL1A1 Sp1 binding site polymorphism on arterial pulse wave velocity: an index of compliance.

Abstract: -Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-alpha1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.6+/-1.6 years). COL1A1 genotypes were determined using polymerase chain reaction and digestion by restriction enzyme Bal1. Arterial pulse wave velocities were measured in 3 segments, aortoiliac (PWVA), aortoradial (PWVB), and aorto-dorsalis-pedis (PWVF), as an index of compliance using a noninvasive optical method. Data were available for 455 subjects. The sample was in Hardy-Weinberg equilibrium with genotype distributions and allele frequencies that were not significantly different from those reported previously. The T allele frequency was 0.22 (95% confidence interval, 0.19 to 0.24). Two hundred eighty-three (62.2%) subjects were genotype GG, 148 (35.5%) subjects were genotype GT, and 24 (5.3%) subjects were genotype TT. A comparison of GG homozygotes with GT and TT individuals demonstrated a statistically significant association with arterial compliance: PWVF 4.92+/-0.03 versus 5.06+/-0.05 m/s (ANOVA, P=0.009), PWVB 4.20+/-0.03 versus 4.32+/-0.04 m/s (ANOVA, P=0.036), and PWVA 3.07+/-0.03 versus 3.15+/-0.03 m/s (ANOVA, P=0.045). The effects of genotype were independent of age, gender, smoking, mean arterial pressure, body mass index, family history of hypertension, and activity scores. We report an association between the COL1A1 gene polymorphism and arterial compliance. Alterations in arterial collagen type 1A deposition may play a role in the regulation of arterial compliance.