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OBJECTIVE: To examine the long-term cardiovascular consequences of angina in a large epidemiological study. DESIGN: Prospective cohort study conducted between 1972 and 1976 with 20 years of follow-up (the Renfrew-Paisley Study). SETTING: Renfrew and Paisley, West Scotland, UK. PARTICIPANTS: 7048 men and 8354 women aged 45-64 years who underwent comprehensive cardiovascular screening at baseline, including the Rose Angina Questionnaire and electrocardiography (ECG). MAIN OUTCOME MEASURES: All deaths and hospitalisations for cardiovascular reasons occurring over the subsequent 20 years, according to the baseline Rose angina score and baseline ECG. RESULTS: At baseline, 669 (9.5%) men and 799 (9.6%) women had angina on Rose Angina Questionnaire. All-cause mortality for those with Rose angina was 67.7% in men and 43.3% in women at 20 years compared with 45.4% and 30.4%, respectively, in those without angina (p<0.001). Values are expressed as hazards ratio (HR) (95% confidence interval (CI). In a multivariate analysis, men with Rose angina had an increased risk of cardiovascular death or hospitalisation (1.49 (1.33 to 1.66), myocardial infarction (1.63 (1.41 to 1.85)) or heart failure (1.54 (1.13 to 2.10)) compared with men without angina. The corresponding HR (95% CI) for women were 1.38 (1.23 to 1.55), 1.56 (1.31 to 1.85) and 1.92 (1.44 to 2.56). An abnormality on the electrocardiogram (ECG) increased risk further, and both angina and an abnormality on the ECG increased risk most of all compared with those with neither angina nor ischaemic changes on the ECG. Compared with men, women with Rose angina were less likely to have a cardiovascular event (0.54 (0.46 to 0.64)) or myocardial infarction (0.44 (0.35 to 0.56)), although there was no sex difference in the risk of stroke (1.11 (0.75 to 1.65)), atrial fibrillation (0.84 (0.38 to 1.87)) or heart failure (0.79 (0.51 to 1.21)). CONCLUSIONS: Angina in middle age substantially increases the risk of death, myocardial infarction, heart failure and other cardiovascular events. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate how carboxyhaemoglobin concentration is related to smoking habit and to assess whether carboxyhaemoglobin concentration is related to mortality. DESIGN: Prospective cohort study. SETTING: Residents of the towns of Renfrew and Paisley in Scotland. PARTICIPANTS: The whole Renfrew/Paisley study, conducted between 1972 and 1976, consisted of 7048 men and 8354 women aged 45-64 years. This study was based on 3372 men and 4192 women who were screened after the measurement of carboxyhaemoglobin concentration was introduced about halfway through the study. MAIN OUTCOME MEASURES: Deaths from coronary heart disease (CHD), stroke, chronic obstructive pulmonary disease (COPD), lung cancer, and all causes in 25 years after screening. RESULTS: Carboxyhaemoglobin concentration was related to self reported smoking and for each smoking category was higher in participants who reported inhaling than in those who reported not inhaling. Carboxyhaemoglobin concentration was positively related to all causes of mortality analysed (relative rates associated with a 1 SD (2.93) increase in carboxyhaemoglobin for all causes, CHD, stroke, COPD, and lung cancer were 1.26 (95% confidence interval (CI) 1.19 to 1.34), 1.19 (95% CI 1.13 to 1.26), 1.19 (95% CI 1.13 to 1.26), 1.64 (95% CI 1.47 to 1.84), and 1.69 (95% CI 1.60 to 1.79), respectively). Adjustment for self reported cigarette smoking attenuated the associations but they remained relatively strong. CONCLUSIONS: Self reported smoking data were validated by the objective measure of carboxyhaemoglobin concentration. Since carboxyhaemoglobin concentration remained associated with mortality after adjustment for smoking, carboxyhaemoglobin seems to capture more of the risk associated with smoking tobacco than does self reported tobacco consumption alone. Analysing mortality by self reported cigarette smoking underestimates the strength of association between smoking and mortality. [ABSTRACT FROM AUTHOR]

Background: The primary prevention of cardiovascular disease involves using the Framingham risk score to identify high risk patients and then prescribe preventive treatments.Aim: To examine the performance of the Framingham risk score in different socioeconomic groups in a population with high rates of cardiovascular disease.Design Of Study: A prospective study.Setting: West of Scotland.Method: The observed 10-year cardiovascular disease and coronary heart disease mortality rates in 5626 men and 6678 women free from cardiovascular disease from the Renfrew/Paisley Study were compared with predicted rates, stratified by socioeconomic class and by area deprivation score.Results: The ratio of predicted to observed cardiovascular mortality rate in the 12 304 men and women with complete risk factor information was 0.56 (95% confidence interval [CI] = 0.52 to 0.60), a relative underestimation of 44%. Cardiovascular disease mortality was underestimated by 48% in manual participants (predicted over observed = 0.52, 95% CI = 0.48 to 0.56) compared to 31% in the non-manual participants (predicted over observed = 0.69, 95% CI = 0.60 to 0.81, P = 0.0005). Underestimation was also worse in participants from deprived areas (P = 0.0017). Only 4.8% of individuals had a 10-year cardiovascular risk of >40% (equivalent to >30% 10-year coronary risk), and 81% of deaths occurred in the rest. If the Framingham score had been recalibrated for manual and non-manual members of this population, an additional 3611 individuals mainly from manual social classes would have reached the treatment threshold.Conclusion: Currently recommended risk scoring methods underestimate risk in socioeconomically deprived individuals. The likely consequence is that preventive treatments are less available to the most needy. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: Transient ischaemic attack (TIA) is often a precursor to stroke, so identification of people experiencing TIA could assist in stroke prevention by indicating those at high risk of stroke who would benefit most from intervention for other stroke risk factors. The objective of this study was to investigate whether answers to a simple questionnaire for TIA could predict the occurrence of stroke in the following 20 years. DESIGN: Prospective cohort study, conducted between 1972 and 1976, with 20 years of follow up. SETTING: Renfrew and Paisley, Scotland. PARTICIPANTS: 7052 men and 8354 women aged 45-64 years at the time of screening completed a questionnaire and attended a physical examination. The questionnaire asked participants if they had ever, without warning, suddenly lost the power of an arm, suddenly lost the power of a leg, suddenly been unable to speak properly or suddenly lost consciousness. These four questions were taken as indicators of TIA and were related to subsequent stroke mortality or hospital admission. MAIN RESULTS: For women, each question was significantly related to stroke risk, whereas for men only the question on loss of power of arm was significantly related to stroke risk. Men and women answering two or more questions positively had double the relative rate of stroke compared with men and women answering none of the questions positively, even after adjusting for other risk factors for stroke. CONCLUSIONS: A simple questionnaire for TIA could help predict stroke over 20 years of follow up. Targeting men and women who report TIA with early treatment could help to prevent strokes from occurring. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study investigated stroke differentials by socioeconomic position in adulthood. METHODS: The relation of risk of stroke to deprivation category and social class was assessed among 6955 men and 7992 women who were aged 45 to 64 years and had been screened in 1972 to 1976. RESULTS: A total of 594 men and 677 women had a hospital admission for stroke or died from stroke. There were large differences in stroke by deprivation category or social class. Adjustment for risk factors (smoking, blood pressure, height, respiratory function, body mass index, cholesterol, diabetes, and preexisting heart disease) attenuated these differences. CONCLUSIONS: Risk factors for stroke can explain some of the socioeconomic differences in stroke risk. Women living in the most deprived areas seem particularly at risk of stroke. [ABSTRACT FROM AUTHOR]

Background: In all 8353 women and 7058 men aged 45-64 took part in the Renfrew/Paisley survey in 1972-1976. They formed a prospective cohort study of a general population in the West of Scotland; an area with high ischaemic heart disease (IHD) mortality rates. The objective of this study was to investigate three indicators of pre-existing IHD and determine how they predicted subsequent IHD mortality in females compared with males.Methods: Pre-existing IHD was ascertained by the Rose Angina questionnaire, a question on severe chest pain indicating evidence of previous IHD and an electrocardiogram at a screening examination. Mortality information for a 15-year follow-up period was available.Results: Pre-existing IHD was higher at older ages and was less common in women than men. The risks of IHD mortality were doubled for those with a single cardiovascular indicator compared to those without, and were increased to fourfold for those with two or more indicators. Indicators of pre-existing IHD had high specificity and low sensitivity for subsequent IHD mortality in both women and men, and the positive predictive values for women in the oldest age group were similar to those for men in the youngest age group.Conclusions: Each indicator of pre-existing IHD was a useful predictor of subsequent IHD mortality in both women and men, even though IHD mortality rates were lower in women. The indicators obtained by questionnaire could be implemented in the primary health care setting to identify quickly those at risk who would benefit from further investigation and intervention. [ABSTRACT FROM AUTHOR]

Background: Limited evidence exists on how temperature increases are associated with hospital visits from alcohol- and substance-related disorders, despite plausible behavioral and physiological pathways., Methods: In the present study, we implemented a case-crossover design, which controls for seasonal patterns, long-term trends, and non- or slowly-varying confounders, with distributed lag non-linear temperature terms (0-6 days) to estimate associations between daily ZIP Code-level temperature and alcohol- and substance-related disorder hospital visit rates in New York State during 1995-2014. We also examined four substance-related disorder sub-causes (cannabis, cocaine, opioid, sedatives)., Results: Here we show that, for alcohol-related disorders, a daily increase in temperature from the daily minimum (-30.1 °C (-22.2 °F)) to the 75th percentile (18.8 °C (65.8 °F)) across 0-6 lag days is associated with a cumulative 24.6% (95%CI,14.6%-34.6%) increase in hospital visit rates, largely driven by increases on the day of and day before hospital visit, with an association larger outside New York City. For substance-related disorders, we find evidence of a positive association at temperatures from the daily minimum (-30.1 °C (-22.2 °F)) to the 50th percentile (10.4 °C (50.7 °F)) (37.7% (95%CI,27.2%-48.2%), but not at higher temperatures. Findings are consistent across age group, sex, and social vulnerability., Conclusions: Our work highlights how hospital visits from alcohol- and substance-related disorders are currently impacted by elevated temperatures and could be further affected by rising temperatures resulting from climate change. Enhanced social infrastructure and health system interventions could mitigate these impacts., (© 2023. Springer Nature Limited.)

Background: During the last few years, the continuous emergence of new psychoactive substances (NPS) has become an important public health challenge. The use of NPS has been rising in two different ways: buying and consuming NPS knowingly and the presence of NPS in traditional drugs as adulterants. The rise of NPS use is increasing the number of different substances in the market to an extent impossible to study with current scientific methodologies. This has caused a remarkable absence of necessary information about newer drug effects on people who use drugs, mental health professionals, and policy makers. Current scientific methodologies have failed to provide enough data in the timeframe when critical decisions must be made, being not only too slow but also too square. Last but not least, they dramatically lack the high resolution of phenomenological details., Objective: This study aims to characterize a population of e-psychonauts and the subjective effects of the NPS they used during the study period using a new, internet-based, fast, and inexpensive methodology. This will allow bridging an evidence gap between online surveys, which do not provide substance confirmation, and clinical trials, which are too slow and expensive to keep up with the new substances appearing every week., Methods: To cover this purpose, we designed a highly personalized, observational longitudinal study methodology. Participants will be recruited from online communities of people who use NPS, and they will be followed online by means of a continuous objective and qualitative evaluation lasting for at least 1 year. In addition, participants will send samples of the substances they intend to use during that period, so they can be analyzed and matched with the effects they report on the questionnaires., Results: The research protocol was approved by the Institutional Review Board of the Hospital del Mar Research Institute on December 11, 2018. Data collection started in August 2019 and was still ongoing when the protocol was submitted (September 2020). The first data collection period of the study ended in October 2020. Data analysis began in November 2020, and it is still ongoing. The authors expect to submit the first results for publication by the end of 2021. A preliminary analysis was conducted when the manuscript was submitted and was reviewed after it was accepted in February 2021., Conclusions: It is possible to conduct an institutional review board-approved study using this new methodology and collect the expected data. However, the meaning and usefulness of these data are still unknown., International Registered Report Identifier (irrid): DERR1-10.2196/24433., (©Marc Grifell, Guillem Mir Fuster, Mireia Ventura Vilamala, Liliana Galindo Guarín, Xoán Carbón Mallol, Carl L Hart, Víctor Pérez Sola, Francesc Colom Victoriano. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.07.2021.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objective: Pathological lying, originally called "pseudologia phantastica," has an established history within clinical practice and literature, although it has not been recognized as a psychological disorder within major nosological systems. With the movement in psychological sciences toward theory-driven, empirically supported diagnoses, the current study sought to empirically test whether pathological lying aligned with nosological definitions and could be defined as a diagnostic entity., Methods: A total of 807 people were recruited (January to October of 2019) from various mental health forums, social media, and a university. Of those recruited, 623 completed the study. Participants responded to a lie frequency prompt, questionnaires about lying behavior, the Lying in Everyday Situations Scale, the Distress Questionnaire-5, and demographic questions., Results: Of the participants, 13% indicated that they self- identified or that others had identified them as pathological liars (telling numerous lies each day for longer than 6 months). People who identified as pathological liars reported greater distress, impaired functioning, and more danger than people not considered pathological liars. Pathological lying seemed to be compulsive, with lies growing from an initial lie, and done for no apparent reason., Conclusions: The evidence supports establishment of pathological lying as a distinct diagnostic entity. A definition of pathological lying, etiological considerations, and recommendations for future research and practice are presented., (© 2020 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC. on behalf of the American Psychiatric Association.)

Exaggerations of the detrimental impact of recreational drug use on the human brain have bolstered support for draconian drug policies and have been used to justify police brutality against Black people. This situation has led to disproportionately high Black incarceration rates and countless Black deaths. Here, I offer solutions to remedy this multi-century maltreatment of Black people., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite limited data demonstrating pronounced negative effects of prenatal cannabis exposure, popular opinion and public policies still reflect the belief that cannabis is fetotoxic. Methods: This article provides a critical review of results from longitudinal studies examining the impact of prenatal cannabis exposure on multiple domains of cognitive functioning in individuals aged 0 to 22 years. A literature search was conducted through PsycINFO, PubMed, and Google Scholar. Articles were included if they examined the cognitive performance of offspring exposed to cannabis in utero . Results: An examination of the total number of statistical comparisons ( n = 1,001) between groups of participants that were exposed to cannabis prenatally and non-exposed controls revealed that those exposed performed differently on a minority of cognitive outcomes (worse on <3.5 percent and better in <1 percent). The clinical significance of these findings appears to be limited because cognitive performance scores of cannabis-exposed groups overwhelmingly fell within the normal range when compared against normative data adjusted for age and education. Conclusions: The current evidence does not suggest that prenatal cannabis exposure alone is associated with clinically significant cognitive functioning impairments., (Copyright © 2020 Torres, Medina-Kirchner, O'Malley and Hart.)

The allosteric regulation of protein function proves important in many life-sustaining processes. In plant photosynthesis, LHCII, the major antenna complex of Photosystem II, employs a delicate switch between light harvesting and photoprotective modes. The switch is triggered by an enlarged pH gradient (ΔpH) across the thylakoid membranes. Using molecular simulations and quantum calculations, we show that ΔpH can tune the light-harvesting potential of the antenna via allosteric regulation of the excitonic coupling in chlorophyll-carotenoid pairs. To this end, we propose how the LHCII excited state lifetime is coupled to the environmental conditions. In line with experimental findings, our theoretical model provides crucial evidence toward the elucidation of the photoprotective switch of higher plants at an all-atom resolution.

Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.

Objective: Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring., Design: Cross-sectional general population survey., Setting: Scotland., Participants: 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45-64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30-59 years surveyed in 1996., Main Measures: Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight., Results: Regression coefficients for BMI associations between father-son (0.30) and mother-daughter (0.33) were greater than father-daughter (0.23) or mother-son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m(2). Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons., Conclusions: There are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic syndrome. A possible epigenetic mechanism linking maternal smoking to obesity and metabolic syndrome in offspring is proposed. Individuals with family histories of obesity should be targeted from an early age to prevent obesity and complications., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: population ageing challenges the sustainability of healthcare provision., Objective: to investigate occupational class differences in hospital use in women aged 80+ years., Methods: a total of 8,353 female residents, aged 45-64, took part in the Renfrew and Paisley prospective cohort study in 1972-76. Information on general and mental health hospital discharges was provided from computerised linkage with the Scottish Morbidity Records data to 31 December 2012. Numbers of admissions and bed-days after the 80th birthday were calculated for all and specific causes. Rate ratios by occupational class were calculated using negative binomial regression analysis, adjusting for age and a range of risk factors., Results: four thousand and four hundred and seven (56%) women survived to age 80 and had 17,563 general admissions thereafter, with a mean stay of 19.4 days. There were no apparent relationships with occupational class for all general admissions, but lower occupational class was associated with higher rate ratios for coronary heart disease and stroke and lower rate ratios for cancer. Adjustment for risk factors could not fully explain the raised rate ratios. Bed-day use was higher in lower occupational classes, especially for stroke. There were strong associations with mental health admissions, especially dementia. Compared with the highest occupational class, admission rate ratios for dementia were higher for the lowest occupational class (adjusted rate ratio = 2.60, 95% confidence interval 1.79-3.77)., Conclusion: in this population, there were no socio-economic gradients seen in hospital utilisation for general admissions in old age. However, occupational class was associated with mental health admissions, coronary heart disease, stroke and cancer., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Adult height is known to be inversely related to coronary heart disease (CHD) risk. We sought to investigate transgenerational influence of parental height on offspring's CHD risk., Methods: Parents took part in a cardiorespiratory disease survey in two Scottish towns during the 1970s, in which their physical stature was measured. In 1996, their offspring were invited to participate in a similar survey, which included an electrocardiogram recording and risk factor assessment., Results: A total of 2306 natural offspring aged 30-59 years from 1456 couples were subsequently flagged for notification of mortality and followed for CHD-related hospitalizations. Taller paternal and/or maternal height was associated with socio-economic advantage, heavier birthweight and increased high-density lipoprotein cholesterol in offspring. Increased height in fathers, but more strongly in mothers (risk ratio for 1 SD change in maternal height = 0.85; 95% confidence interval: 0.76 to 0.95), was associated with a lower risk of offspring CHD, adjusting for age, sex, other parental height and CHD risk factors., Conclusion: There is evidence of an association between taller parental, particularly maternal, height and lower offspring CHD risk. This may reflect an influence of early maternal growth on the intrauterine environment provided for her offspring.

Objective: This study investigated the association between long-term exposure to black smoke (BS) air pollution and mortality in two related Scottish cohorts with 25 years of follow-up., Methods: Risk factors were collected during 1970-1976 for 15331 and 6680 participants in the Renfrew/Paisley and Collaborative cohorts respectively. Exposure to BS during 1970-1979 was estimated by inverse-distance weighted averages of observed concentrations at monitoring sites and by two alternative spatial modelling approaches which included local air quality predictors (LAQP)., Results: Consistent BS-mortality associations (per 10 μg m(-3) increment in 10-year average BS) were observed in the Renfrew/Paisley cohort using LAQP-based exposure models (all-cause mortality HR 1.10 (95% CI 1.04 to 1.17); cardiovascular HR 1.11 (1.01 to 1.22); ischaemic heart disease HR 1.13 (1.02 to 1.25); respiratory HR 1.26 (1.02 to 1.28)). The associations were largely unaffected by additional adjustment for area-level deprivation category. A less consistent and generally implausible pattern of cause-specific BS-mortality associations was found for inverse-distance averaging of BS concentrations at nearby monitoring sites. BS-mortality associations in the Collaborative cohort were weaker and not statistically significant., Conclusions: The association between mortality and long-term exposure to BS observed in the Renfrew/Paisley cohort is consistent with hypotheses of how air pollution may affect human health. The dissimilarity in pollution-mortality associations for different exposure models highlights the critical importance of reliable estimation of exposures on intraurban spatial scales to avoid potential misclassification bias.

Background: Air pollution-mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales., Objective: We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure-mortality associations in cohort participants and with short-term exposure-mortality associations in the general population from which the cohorts were selected., Methods: We assessed short-to-medium-term exposure-mortality associations in the Renfrew-Paisley and Collaborative cohorts (using nested case-control data sets), and compared them with long-term exposure-mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium-term exposure-mortality associations in the general population (using time-series analyses)., Results: For the Renfrew-Paisley cohort (15,331 participants), BS exposure-mortality associations were observed in nested case-control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m³ increases in 3-day lag BS, respectively}. Exposure-mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: -0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m³ increases in 31-day BS in case-control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m³ increase in geometic mean BS for 1970-1979, in survival analysis]., Conclusions: After adjusting for individual-level exposure and potential confounders, short-term exposure-mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure-mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures.

3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT(2A) receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT(2A) receptors. Positron emission tomography studies using the SERT ligand [¹¹C]DASB and the 5-HT(2A) receptor ligand [¹¹C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT(2A) receptor availability (binding potential, BP(ND)) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BP(ND) and higher 5-HT(2A) receptor BP(ND) in cortical, but not subcortical regions. Decreased SERT BP(ND) was regionally associated with upregulated 5-HT(2A) receptor BP(ND). In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established.

The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy.

Objective: To investigate the relations between causes of death, social position, and obesity in women who had never smoked., Design: Prospective cohort study., Setting: Renfrew and Paisley, Scotland., Participants: 8353 women and 7049 men aged 45-64 were recruited to the Renfrew and Paisley Study in 1972-6. Of these, 3613 women had never smoked and were the focus of this study. They were categorised by occupational class (I and II, III non-manual, III manual, and IV and V) and body mass index groups (normal weight, overweight, moderately obese, and severely obese)., Main Outcome Measures: All cause and cause specific mortality during 28 years of follow-up by occupational class and body mass index, using Cox proportional hazards models adjusted for age and other confounders., Results: The women in lower occupational classes who had never smoked were on average shorter and had poorer lung function and higher systolic blood pressure than women in the higher occupational classes. Overall, 43% (n = 1555) were overweight, 14% (n = 515) moderately obese, and 5% (n = 194) severely obese. Obesity rates were higher in lower occupational classes and much higher in all occupational classes than in current smokers in the full cohort. Half the women died, 51% (n = 916) from cardiovascular disease and 27% (n = 487) from cancer. Relative to occupational class I and II, all cause mortality rates were more than a third higher in occupational classes III manual (relative rate 1.35, 95% confidence interval 1.16 to 1.57) and IV and V (1.34, 1.17 to 1.55) and largely explained by differences in obesity, systolic blood pressure, and lung function. Similar upward gradients were seen for cardiovascular disease and respiratory disease but not for cancer. Mortality rates were highest in severely obese women in the lowest occupational classes., Conclusions: Women who had never smoked and were not obese had the lowest mortality rates, regardless of their social position. Where obesity is socially patterned as in this cohort, it may contribute to health inequalities and increase pressure on health and social services serving more disadvantaged populations.

Background: Smoking and consuming alcohol are both related to increased mortality risk. Their combined effects on cause-specific mortality were investigated in a prospective cohort study., Methods: Participants were 5771 men aged 35-64, recruited during 1970-73 from various workplaces in Scotland. Data were obtained from a questionnaire and a screening examination. Causes of death were all cause, coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking-related cancer. Participants were divided into nine groups according to their smoking status (never, ex or current) and reported weekly drinking (none, 1-14 units and 15 or more). Cox proportional hazards models were used to obtain relative rates of mortality, adjusted for age and other risk factors., Results: In 30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did not drink, men who both smoked and drank 15+ units/week had the highest all-cause mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative rates for CHD mortality were high for current smokers, with a possible protective effect of some alcohol consumption in never smokers. Stroke mortality increased with both smoking and alcohol consumption. Smoking affected respiratory mortality with little effect of alcohol. Adjusting for a wide range of confounders attenuated the relative rates but the effects of alcohol and smoking still remained. Premature mortality was particularly high in smokers who drank 15 or more units, with a quarter of the men not surviving to age 65. 30% of men with manual occupations both smoked and drank 15+ units/week compared with only 13% with non-manual ones., Conclusions: Smoking and drinking 15+ units/week was the riskiest behaviour for all causes of death.

The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (i) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.

Objectives: To analyse the relationship between body mass index (BMI) and liver disease in men and women., Design: The Midspan prospective cohort studies., Participants: The three studies were: Main study, screened in 1965-1968, workplaces across Scotland, the general population of the island of Tiree and mainland relatives; Collaborative study, conducted from 1970 to 1973, 27 workplaces in Glasgow, Clydebank and Grangemouth; Renfrew/Paisley general population study, screened in 1972-1976. After exclusions there were 16 522 men and 10 216 women, grouped by BMI into under/normal weight (< 25 kg m(-2)), overweight (25 to < 30 kg m(-2)) and obese (>or=30 kg m(-2))., Measurements: Relative rates (RRs) of liver disease mortality, subdivided into liver cancer and all other liver disease, by BMI category and per s.d. increase in BMI, followed-up to end 2007. RRs of liver disease from any diagnosis on the death certificate, hospital discharge records or cancer registrations (Collaborative and Renfrew/Paisley studies only 13 027 men and 9328 women). Analyses adjusted for age and study, then other confounders., Results: In total, 146 men (0.9%) and 61 women (0.6%) died of liver disease as main cause. There were strong associations of BMI with liver disease mortality in men (RR per s.d. increase in BMI=1.41 (95% confidence interval 1.21-1.65)). Obese men had more than three times the rate of liver disease mortality than under/normal weight men. Adjustment for other risk factors had very little effect. No substantial or robust associations were observed in women. In all, 325 men (2.5%) and 155 women (1.7%) had liver disease established from any source. Similar positive associations were observed for men, and there was evidence of a relationship in women., Conclusions: BMI is related to liver disease, although not to liver disease mortality in women. The current rise in overweight and obesity may lead to a continuing epidemic of liver disease.

Objective: To investigate whether alcohol consumption and raised body mass index (BMI) act together to increase risk of liver disease., Design: Analysis of data from prospective cohort studies., Setting: Scotland., Participants: Data were from two of the Midspan prospective cohort studies (9559 men): "Main" study 1965-8, participants from workplaces across central belt of Scotland, population of island of Tiree, and mainland relatives, and "Collaborative" study, 1970-3, participants from 27 workplaces in Glasgow, Clydebank, and Grangemouth. Follow-up was to 31 December 2007 (median 29 years, range 0.13-42). We divided participants into nine groups based on measures of body mass index (BMI) (underweight/normal weight <25, overweight 25 to <30, and obese >or=30) and alcohol consumption (none, 1-14, and >or=15 units per week)., Main Outcome Measures: Liver disease morbidity and mortality., Results: 80 (0.8%) men died with liver disease as the main cause and 146 (1.5%) with liver disease as any cause. In the Collaborative study, 196 men (3.3%) had liver disease defined by a death, admission, or cancer registration. BMI and alcohol consumption were strongly associated with liver disease mortality in analyses adjusted for other confounders (P=0.001 and P<0.0001 respectively). Drinkers of 15 or more units per week in any BMI category and obese drinkers had raised relative rates for all definitions of liver disease, compared with underweight/normal weight non-drinkers. Drinkers of 15 or more units per week had adjusted relative rates for liver disease mortality of 3.16 (95% confidence interval 1.28 to 7.8) for underweight/normal weight men, 7.01 (3.02 to 16.3) for overweight, and 18.9 (6.84 to 52.4) for obese men. The relative rate for obese men who consumed 1-14 units per week was 5.3 (1.36 to 20.7). The relative excess risk due to interaction between BMI and alcohol consumption was 5.58 (1.09 to 10.1); synergy index=2.89 (1.29 to 6.47)., Conclusions: Raised BMI and alcohol consumption are both related to liver disease, with evidence of a supra-additive interaction between the two. The occurrence of both factors in the same populations should inform health promotion and public health policies.

A post hoc analysis examined depressive symptoms in regular marijuana smokers interested in nontreatment, laboratory studies, and marijuana-dependent treatment-seekers considering clinical trial participation. Among marijuana-dependent treatment-seeking patients screened for a clinical trial, the mean Beck Depression Inventory Score (BDI) was significantly higher than for marijuana-using volunteers screened for nontreatment laboratory studies. Mean self-reported baseline marijuana use was not significantly different between groups, and BDI score was not correlated with use. Although the methods by which the two groups were selected influenced their characteristics (i.e., treatment-seekers are more likely to be experiencing some degree of clinical distress), it is notable that treatment-seeking, and not marijuana use per se, is associated with significantly higher rates of depression.

Background: Overconsumption of alcohol affects health. Data from men from the West of Scotland Collaborative study were analysed to see how reported alcohol was related to acute and mental health hospital admissions., Methods: Men (N = 5772) from a prospective cohort study located in 27 workplaces in West and Central Scotland were screened when aged 35-64 in 1970-3. The number of acute and mental health admissions and bed-days were calculated by alcohol category (none, 1-7, 8-14, 15-21, 22-34 and 35 or more units per week) to the end of 2005. Specific causes were coronary heart disease (CHD), stroke, respiratory diseases and alcohol-related., Results: Men who consumed 22 or more units per week had a 20% higher rate of acute admissions than non-drinkers. The number of bed-days were higher for men drinking eight or more units and increased with consumption, with the highest category having a 58% higher rate of bed-days than non-drinkers. Non-drinkers had the highest admissions for CHD. For stroke, drinkers of 15 or more units had higher admissions and higher number of bed-days and these increased with increasing consumption. Respiratory admissions were higher for drinkers of 22 or more units and bed-days were higher for drinkers of 15 or more units. Alcohol-related admissions and number of bed-days generally increased with consumption. Mental health admissions and number of bed-days were raised for drinkers of 22 or more units with a suggestion of a J-shaped relationship., Conclusion: Alcohol consumption has a substantial effect on acute and mental health admissions and bed-days.

Aims: The aim of this study was to investigate relationships between alcohol consumption and social mobility in a cohort study in Scotland., Methods: 1040 sons and 1298 daughters aged 30-59 from 1477 families reported their alcohol consumption from which was derived: weekly units (1 UK unit being 8 g ethanol), exceeding daily or weekly limits, binge drinking and consuming alcohol on 5+ days per week. Own and father's social class were available enabling social mobility to be investigated., Results: More downwardly mobile men exceeded the weekly limit, the daily limit, were defined as binge drinkers and drank the most units per week of the four social mobility groups. Stable non-manual women were more likely to consume alcohol on 5+ days a week but very few were binge drinkers. Stable non-manual and upwardly mobile men and women were more likely to drink wine, and downwardly mobile men to drink beer., Conclusions: Downward mobility was associated with less favourable alcohol behaviours, especially in men. Wine consumption was more closely related to the social mobility groups than beer and spirits consumption. Drinking patterns could both influence and be influenced by social mobility.

Objective: To assess the impact of tobacco smoking on the survival of men and women in different social positions., Design: A cohort observational study., Setting: Renfrew and Paisley, two towns in west central Scotland., Participants: 8353 women and 7049 men aged 45-64 years recruited in 1972-6 (almost 80% of the population in this age group). The cohort was divided into 24 groups by sex (male, female), smoking status (current, former, or never smokers), and social class (classes I + II, III non-manual, III manual, and IV + V) or deprivation category of place of residence., Main Outcome Measure: Relative mortality (adjusted for age and other risk factors) in the different groups; Kaplan-Meier survival curves and survival rates at 28 years., Results: Of those with complete data, 4387/7988 women and 4891/6967 men died over the 28 years. Compared with women in social classes I + II who had never smoked (the group with lowest mortality), the adjusted relative mortality of smoking groups ranged from 1.7 (95% confidence interval 1.3 to 2.3) to 4.2 (3.3 to 5.5). Former smokers' mortalities were closer to those of never smokers than those of smokers. By social class (highest first), age adjusted survival rates after 28 years were 65%, 57%, 53%, and 56% for female never smokers; 41%, 42%, 33%, and 35% for female current smokers; 53%, 47%, 38%, and 36% for male never smokers; and 24%, 24%, 19%, and 18% for male current smokers. Analysis by deprivation category gave similar results., Conclusions: Among both women and men, never smokers had much better survival rates than smokers in all social positions. Smoking itself was a greater source of health inequality than social position and nullified women's survival advantage over men. This suggests the scope for reducing health inequalities related to social position in this and similar populations is limited unless many smokers in lower social positions stop smoking.

Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and 'positive' subjective effects, with peaks occurring approximately 5-15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses.

The aim of this study was to evaluate midparental BMI among intergenerational factors associated with obesity in adult offspring. The data was from an unusual two-generational observational design of 1,477 married couples from Renfrew and Paisley in Scotland who were aged 45-64 years when screened in 1972-1976, and 1,040 sons and 1,298 daughters aged 30-59 years when screened in 1996. BMI was categorized as normal (< 25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (> or = 30 kg/m(2)) in offspring and parents. Midparental BMI was defined as the mean of the mother's and father's BMI. Low physical activity, nonsmoking status, higher cholesterol level, and manual social class were all associated with increased BMI in offspring. The effect of reported dietary intake was less clear. Offspring of obese parents (defined by midparental BMI) were over four times more likely to be obese than offspring of normal weight parents. Midparental BMI had a strong effect on offspring BMI, independent of social class, smoking habit, physical activity, and reported dietary intake. Adding midparental BMI to the regression model more than doubled the explained variation of offspring BMI from 7.7 to 17%. Every 1 kg/m(2) increment in midparental BMI was associated with a BMI greater by 0.51 kg/m(2) in offspring. We conclude that midparental BMI is a useful simple tool to predict offspring BMI. Whether it represents genetic or environmental family effects, it is easily ascertained by the individual and could be used in health promotion and clinical settings to target individuals who are at increased risk of becoming obese.

Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400 mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment-seeking cocaine-dependent individuals (n=8). Cocaine significantly increased self-administration, subjective-effect ratings, and cardiovascular measures; modafinil at both doses (200 and 400 mg/day) markedly attenuated these effects. These findings agree with data from previous human laboratory and clinical investigations of modafinil as a potential cocaine abuse treatment medication. Thus, our data support the potential of modafinil as a pharmacotherapy for cocaine dependence.

Objectives: Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep., Methods: HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Delta9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition., Results: As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, "good drug effect") with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep., Conclusions: These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.

Objectives: To investigate how loss of a spouse affects mortality risk in the bereaved partner., Design and Setting: Prospective cohort study in Renfrew and Paisley in Scotland., Participants: 4395 married couples aged 45-64 years when the study was carried out between 1972 and 1976., Methods: The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow-up period, so it was considered as a time-dependent exposure variable and the Cox proportional hazards model for time-dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non-bereaved spouses and adjusted for confounding variables., Main Outcome Measures: Causes of death to 31 March 2004., Results: Bereaved participants were at higher risk than non-bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking-related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement., Conclusions: Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death.

Background: Because overweight and obesity are associated with comorbidities, increasing levels of overweight and obesity may impact on hospital use., Methods: Body mass index (BMI) in middle age was related to acute hospital use in 7036 men and 8327 women from the Renfrew/Paisley prospective cohort study in Scotland. Participants in this general population study were examined between 1972 and 1976 when aged 45-64 years. Acute hospital admissions and bed days per 1000 person-years were calculated by the World Health Organization BMI categories in the follow-up period to 31 March 2004., Results: Underweight and normal weight men had lower-than-expected admission rates, and overweight and obese men had higher-than-expected admission rates. Obese men had higher-than-expected bed day rates. For women, there was a U-shaped relationship with admission rate, with normal weight women having the lowest admission rate and underweight and obese women having similar high rates. Underweight and obese women had higher-than-expected bed day rates., Conclusions: Participants who were obese in midlife had more-than-expected acute hospital admissions and in particular more bed days. With levels of obesity increasing since this study was started in the 1970s, if these patterns persist, there may be increasing demand on health service resources.

Objective: To examine the effect of reverse causality and confounding on the association of BMI with all-cause and cause-specific mortality., Research Methods and Procedures: Data from two large prospective studies were used. One (a community-based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972-1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970-1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow-up period was 28 to 34 years., Results: In age-adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m(2)) and mortality, and weak to modest associations between obesity (BMI > or =30 kg/m(2)) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never-smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all-cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never-smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease., Discussion: These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all-cause and cause-specific mortality, and in particular with cardiovascular disease mortality.

Background: There are few data describing the effect of socioeconomic deprivation on the risk of developing heart failure (HF)., Aims: To examine the relationship between socioeconomic deprivation and hospitalisation with HF over 20 years., Methods: Between 1972 and 1976, 15,402 individuals, aged 45-64 years, residing in two towns in Scotland, underwent cardiovascular screening. We report hospitalisations with HF over the subsequent 20 years according to Carstairs deprivation category and Social Class., Results: Following screening, 628 men and women (4.1%) were hospitalised with a primary diagnosis of HF. There was a gradient in the risk of HF hospitalisation with increasing socioeconomic deprivation (P=0.003). Of the most deprived individuals, 6.4% were hospitalised for HF compared to 3.5% of the most affluent group. Cox-proportional Hazard models showed that independent of age, sex and baseline risk factors for cardio-respiratory status, greater socioeconomic deprivation increased the risk of HF admission (P<0.001, overall). The adjusted risk of admission for HF was 39% greater in the most versus least deprived subjects (RR 1.39 95% CI 1.04-2.01; P=0.04)., Conclusion: These data show a link between social deprivation and the risk of developing HF, irrespective of baseline cardio-respiratory status and cardiovascular risk factors.

Background: This study examined whether psychological distress might be a predictor of chronic obstructive pulmonary disease (COPD)., Method: The relation between psychological distress at baseline, measured by the general health questionnaire (GHQ), and chronic bronchitis three years later, as measured by the Medical Research Council (MRC) bronchitis questionnaire and forced expiratory flow in one second (FEV(1)), was examined in 1682 men and 2203 women from the Renfrew and Paisley (MIDSPAN) study. The analyses were run on men and women separately and adjustments were made for age, socioeconomic position, and lung function at baseline (FEV(1)). People with chronic diseases at baseline were then excluded to give a "healthy" baseline cohort. The effect of psychological distress on individual components of the MRC bronchitis questionnaire and FEV(1) was also assessed., Results: In multivariate analyses of the whole cohort baseline psychological distress in women was associated with reduced FEV(1) at follow up (OR 1.31 95% CI 1.0 to 1.73) after adjustment. In women, in the healthy cohort, psychological distress was associated with chronic bronchitis (OR 2.00, 95% CI 1.16 to 3.46), symptoms of bronchial infection (OR 2.14, 95% CI 1.44 to 3.19), symptoms of breathlessness (OR 3.02, 95% CI 1.99 to 4.59), and reduced FEV(1) (OR 1.62, 95% CI 1.13 to 2.32). In men psychological distress predicted symptoms of bronchial infection (OR 2.09, 95% CI 1.28 to 3.42)., Conclusion: This study supports research suggesting that psychological distress is associated with COPD and shows that psychological distress predicts COPD in women. The robustness of the association and the exact mechanism requires further investigation.

Preclinical and clinical studies suggest that GABAB receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone. The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence. Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one 5 dollars merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group. The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users.