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Gale C.R.,Center for Cognitive Ageing and Cognitive Epidemiology | Gale C.R.,University of Edinburgh | Gale C.R.,Southampton General Hospital | Batty G.D.,Center for Cognitive Ageing and Cognitive Epidemiology | And 11 more authors.
Psychosomatic Medicine | Year: 2015

To examine the relation between reaction time in adolescence and subsequent symptoms of anxiety and depression and investigate the mediating role of sociodemographic measures, health behaviors, and allostatic load. Methods Participants were 705 members of the West of Scotland Twenty-07 Study. Choice reaction time was measured at age 16. At age 36 years, anxiety and depression were assessed with the 12-item General Health Questionnaire (GHQ) and the Hospital Anxiety and Depression Scale (HADS), and measurements were made of blood pressure, pulse rate, waist-to-hip ratio, and total and high-density lipoprotein cholesterol, C-reactive protein, albumin, and glycosolated hemoglobin from which allostatic load was calculated. Results In unadjusted models, longer choice reaction time at age 16 years was positively associated with symptoms of anxiety and depression at age 36 years: for a standard deviation increment in choice reaction time, regression coefficients (95% confidence intervals) for logged GHQ score, and square-root-transformed HADS anxiety and depression scores were 0.048 (0.016-0.080), 0.064 (0.009-0.118), and 0.097 (0.032-0.163) respectively. Adjustment for sex, parental social class, GHQ score at age 16 years, health behaviors at age 36 years and allostatic load had little attenuating effect on the association between reaction time and GHQ score, but weakened those between reaction time and the HADS subscales. Part of the effect of reaction time on depression was mediated through allostatic load; this mediating role was of borderline significance after adjustment. Conclusions Adolescents with slower processing speed may be at increased risk for anxiety and depression. Cumulative allostatic load may partially mediate the relation between processing speed and depression. © 2015 by the American Psychosomatic Society.


News Article | April 13, 2016
Site: www.biosciencetechnology.com

Neuroticism, a personality trait related to depression, anxiety and even heart disease, can be linked to nine new distinct gene-associations according to international research led by the University of Glasgow. The study, which is published today in Molecular Psychiatry, was co-led by Professor Daniel Smith from the Institute of Health and Wellbeing and included researchers from the Universities of Edinburgh, Cardiff and Queensland, Australia. The existence of these genetic associations could indicate a person’s predisposition to the personality trait neuroticism. The authors focused on neuroticism as it is the personality trait most closely associated with mental illness and physical health problems. People who have high neuroticism levels tend toward depression and anxiety. They also tend to have worse physical health, with links to conditions such as obesity and heart disease. The research represents the largest genetic study of a personality trait ever undertaken, and improves our understanding of people’s personality differences, and why some are more predisposed to mental health problems than others. The study tested more than 100,000 individuals from the UK Biobank cohort, the Generation Scotland sample and the Queensland Institute of Medical Research sample. Professor Smith said: “As a psychiatrist, this is an exciting discovery because we have identified for the first time genetic risk factors for a personality trait which is of fundamental importance for psychological wellbeing. “This work could open new avenues for future research and for the identification of new treatment approaches for depression and anxiety. It is a first step to understanding the biology and genetic basis of a person’s vulnerability to depression and anxiety.” Although further work is needed to pinpoint the exact DNA changes responsible, the findings potentially indicate the involvement of molecules linking neuroticism with mental illness. One has an important role in managing the body's response to stress, while another influences the function of glutamate – an important brain chemical involved in a range of psychiatric disorders, including schizophrenia, depression and suicide. Professor Ian Deary, from the University of Edinburgh, said, "I have been researching on human personality for almost 30 years. These new results are, at last, a start for our understanding the biological mechanisms that predispose some people to generally feel more anxious and low in mood than others." Professor Michael O’Donovan, from Cardiff University said “this research confirms at a molecular level what epidemiological research has clearly shown to those who are not blinded by prejudice; to understand the origins of psychological traits, the most human of all our characteristics, we have to understand both our genetic inheritance and our environment.” Dr Raliza Stoyanova, Neuroscience & Mental Health Senior Portfolio Developer at the Wellcome Trust, said: “By combining a number of very large studies, including UK Biobank, the researchers have identified new genetic associations for neuroticism - one of the five fundamental personality traits present in all of us. “It will be important for future work to uncover how these genetic links affect brain function, and to pin down whether they increase someone’s chance of developing clinical depression.” The study is published today in the journal Molecular Psychiatry.


Porter D.,University of Glasgow | van Melckebeke J.,University of Glasgow | Dale J.,Wishaw General Hospital | Messow C.M.,Institute of Health and Wellbeing | And 12 more authors.
Lancet (London, England) | Year: 2016

BACKGROUND: Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis.METHODS: This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor-adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patient's and rheumatologist's choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0.6 DAS28-ESR units. This study is registered with ClinicalTrials.gov, number NCT01021735.FINDINGS: Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was -2.6 (SD 1.4) and TNF inhibitor was -2.4 (SD 1.5), with a difference within the prespecified non-inferiority margin of -0.19 (95% CI -0.51 to 0.13; p=0.24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (£9,405 vs £11,523 per patient, p<0.0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0.5462). One patient in each group died during the study.INTERPRETATION: Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months.FUNDING: Arthritis Research UK, Roche. Copyright © 2016 Elsevier Ltd. All rights reserved.


PubMed | Raigmore Hospital, Haywood Hospital, Whytemans Brae Hospital, Western General Hospital and 7 more.
Type: Comparative Study | Journal: Lancet (London, England) | Year: 2016

Tumour necrosis factor (TNF) inhibition and B-cell depletion are highly effective treatments for active rheumatoid arthritis, but so far no randomised controlled trials have directly compared their safety, efficacy, and cost-effectiveness. This study was done to test the hypothesis that using rituximab would be clinically non-inferior and cheaper compared with TNF inhibitor treatment in biological-treatment naive patients with rheumatoid arthritis.This open-label, randomised controlled, non-inferiority trial enrolled patients with active, seropositive rheumatoid arthritis and an inadequate response to synthetic disease modifying anti-rheumatic drugs (DMARDs) from 35 rheumatology departments in the UK. Patients were randomly assigned 1:1 to the rituximab or TNF inhibitor groups with minimisation to account for methotrexate intolerance using a web-based randomisation system. Patients were given intravenous rituximab 1 g on days 1 and 15, and after 26 weeks if they responded to treatment but had persistent disease activity (28 joint count disease activity score [DAS28-ESR] >3.2; rituximab group) or a TNF inhibitor-adalimumab (40 mg subcutaneously every other week) or etanercept (50 mg per week subcutaneously) according to the patients and rheumatologists choice (TNF inhibitor group). Patients could switch treatment in the case of drug-related toxic effects or absence or loss of response. The primary outcome measure was the change in DAS28-ESR between 0 and 12 months in the per-protocol population of patients who were assigned to treatment and remained in follow-up to 1 year. We assessed safety in all patients who received at least one dose of study drug. We also assessed the cost-effectiveness of each strategy. The non-inferiority margin was specified as 0.6 DAS28-ESR units. This study is registered with ClinicalTrials.gov, number NCT01021735.Between April 6, 2009, and Nov 11, 2013, 295 patients were randomly assigned and given either rituximab (n=144) or TNF inhibitor (n=151) treatment. After 12 months, the change in DAS28-ESR for patients assigned to rituximab was -2.6 (SD 1.4) and TNF inhibitor was -2.4 (SD 1.5), with a difference within the prespecified non-inferiority margin of -0.19 (95% CI -0.51 to 0.13; p=0.24). The health-related costs associated with the rituximab strategy were lower than the TNF inhibitor strategy (9,405 vs 11,523 per patient, p<0.0001). 137 (95%) of 144 patients in the rituximab group and 143 (95%) of 151 patients in the TNF inhibitor group had adverse events. 37 serious adverse events occurred in patients receiving rituximab compared with 26 in patients receiving TNF inhibitors, of which 27 were deemed to be possibly, probably, or definitely related to the treatment (15 vs 12, p=0.5462). One patient in each group died during the study.Initial treatment with rituximab is non-inferior to initial TNF inhibitor treatment in patients seropositive for rheumatoid arthritis and naive to treatment with biologicals, and is cost saving over 12 months.Arthritis Research UK, Roche.


Baranidharan G.,Leeds Teaching Hospitals NHS Trust | Baranidharan G.,University of Leeds | Briggs M.,Institute of Health and Wellbeing | Briggs M.,Leeds Beckett University
Surgery (United Kingdom) | Year: 2014

Adequate pain control is vital in perioperative care. Pain affects respiratory and cardiovascular function with knock-on effects on many other organs and systems. Surgery is also recognized as one of the most frequent causes of chronic pain with surgical approach and level of pain experienced being modifiable risk factors for the development of chronic post-surgical pain. Local anaesthetic can be used to facilitate pain relief either by local infiltration or nerve blocks, increased mobility and a better perioperative and postoperative experience for the patients. There are two pharmacological types, esters and amides, that have different uses. Commonly used blocks are brachial plexus block, Bier's block, femoral nerve block, spinal block and epidurals. These can be used alone or in combination with a general anaesthetic. © 2014 Elsevier Ltd. All rights reserved.


MacKenzie M.,University of Glasgow | Reid M.,Institute of Health and Wellbeing | Turner F.,Institute of Health and Wellbeing | Wang Y.,Institute of Health and Wellbeing | And 4 more authors.
Journal of Social Policy | Year: 2012

The concept of systematic inequalities in social and health outcomes has come to form part of contemporary policy discourse. This rhetoric is deployed even in the face of policy decisions widely viewed as iniquitous. Moreover, there is a widespread view, expressed across the political spectrum, that those in more deprived circumstances are less likely than their more affluent counterparts to be in receipt of optimal public services. Such individuals and communities are variously described as excluded, disadvantaged, underserved or hard to reach. Across countries and policy domains the term 'hard to reach' is used to refer to those deemed not to be in optimal receipt of public sector services which are intended to increase some aspect of material, social or physical wellbeing. It is increasingly used in health policy documents which aim to address health inequalities. However, it is an ill-defined and contested term. The purpose of this paper is two-fold. First, it offers a critical commentary on the concept of hard-to-reachness and asks: who are viewed as hard to reach and why? Second, using a case-study of a Scottish health improvement programme that explicitly aims to reach and engage the 'hard to reach' in preventive approaches to cardiovascular disease, it tests the policy and practice implications of the concept. It finds that a lack of conceptual clarity leads to ambiguous policy and practice and argues for possible theoretical refinements. © 2012 Cambridge University Press.


Bergman B.P.,Institute of Health and Wellbeing | Mackay D.F.,Institute of Health and Wellbeing | Pell J.P.,Institute of Health and Wellbeing
Occupational and Environmental Medicine | Year: 2015

Objectives In 2003, it was reported that motor neurone disease was linked to military service in the 1990-1991 Gulf War. A large study in the US confirmed an association with military service but found no association with specific conflicts or length of service. Non-veteran studies have suggested an association with physical activity, smoking and other risk factors. We used data from the Scottish Veterans Health Study to investigate the association between motor neurone disease and military service in UK veterans. Methods Retrospective cohort study of 57 000 veterans born 1945-1985, and 173 000 demographically matched civilians, using Cox proportional hazard models to compare the risk of motor neurone disease overall, and by sex, birth cohort, length of service and year of recruitment. We had no data on smoking prevalence. Results Veterans had an increased risk of motor neurone disease compared with non-veterans (adjusted HR 1.49, 95% CI 1.01 to 2.21, p=0.046). The increase was independent of birth cohort, length or period of service, or year of recruitment. Risk was associated with a history of trauma or road traffic accident in veterans and non-veterans. Conclusions We confirmed an increased risk of motor neurone disease in military veterans, although the absolute risk is extremely low. We found no evidence that the increased risk was associated with any specific conflict. We could not rule out that smoking (and perhaps other lifestyle factors) may be responsible for our findings. Trauma may play a role in the increased risk but further studies are needed.


Bergman B.P.,University of Glasgow | Bergman B.P.,Institute of Health and Wellbeing | Mackay D.F.,University of Glasgow | Smith D.J.,University of Glasgow | Pell J.P.,University of Glasgow
Journal of Clinical Psychiatry | Year: 2016

Objective: We used data from the Scottish Veterans Health Study to examine long-term mental health outcomes in a large cohort of veterans, with a focus on the impact of length of service. Methods: We conducted a retrospective, 30-year cohort study of 56,205 veterans born from 1945 through 1985, including 14,702 who left military service prematurely, and 172,741 people with no record of military service, using Cox proportional hazard models, to examine the association between veteran status and length of service and cumulative risk of mental health disorder. We stratified the veterans by common lengths of service, defining Early Service Leavers as those who had served for less than 2.5 years. Results: There were 2,794 (4.97%) first episodes of any mental health disorder in veterans, compared with 7,779 (4.50%) in nonveterans. The difference was statistically significant for all veterans (adjusted hazard ratio [HR] = 1.21; 95% CI, 1.16-1.27; P 〈 .001). Subgroup analysis showed the highest risk to be in Early Service Leavers (adjusted HR = 1.51; 95% CI, 1.30-1.50; P 〈 .001), including those who failed to complete initial training. The risk reduced with longer service; beyond 9 years of service, risk of mental health disorder was comparable to or lower than that in nonveterans. Conclusions: The veterans at highest risk of mental health disorder were those who did not complete training or minimum engagement, while those with longest service were at reduced risk, suggesting that military service was not causative. The high risk among the earliest leavers may reflect pre-service vulnerabilities not detected at recruitment, which become apparent during early training and lead to early discharge. © Copyright 2016 Physicians Postgraduate Press, Inc.


PubMed | Institute of Cardiovascular and Medical science, University of Glasgow and Institute of Health and Wellbeing
Type: | Journal: International journal of epidemiology | Year: 2016

Policy makers are being encouraged to specifically target sugar intake in order to combat obesity. We examined the extent to which sugar, relative to other macronutrients, was associated with adiposity.We used baseline data from UK Biobank to examine the associations between energy intake (total and individual macronutrients) and adiposity [body mass index (BMI), percentage body fat and waist circumference]. Linear regression models were conducted univariately and adjusted for age, sex, ethnicity and physical activity.Among 132479 participants, 66.3% of men and 51.8% of women were overweight/obese. There was a weak correlation (r=0.24) between energy from sugar and fat; 13% of those in the highest quintile for sugar were in the lowest for fat, and vice versa. Compared with normal BMI, obese participants had 11.5% higher total energy intake and 14.6%, 13.8%, 9.5% and 4.7% higher intake from fat, protein, starch and sugar, respectively. Hence, the proportion of energy derived from fat was higher (34.3% vs 33.4%, P < 0.001) but from sugar was lower (22.0% vs 23.4%, P < 0.001). BMI was more strongly associated with total energy [coefficient 2.47, 95% confidence interval (CI) 2.36-2.55] and energy from fat (coefficient 1.96, 95% CI 1.91-2.06) than sugar (coefficient 0.48, 95% CI 0.41-0.55). The latter became negative after adjustment for total energy.Fat is the largest contributor to overall energy. The proportion of energy from fat in the diet, but not sugar, is higher among overweight/obese individuals. Focusing public health messages on sugar may mislead on the need to reduce fat and overall energy consumption.


PubMed | University of Glasgow and Institute of Health and Wellbeing
Type: Journal Article | Journal: The Journal of clinical psychiatry | Year: 2016

We used data from the Scottish Veterans Health Study to examine long-term mental health outcomes in a large cohort of veterans, with a focus on the impact of length of service.We conducted a retrospective, 30-year cohort study of 56,205 veterans born from 1945 through 1985, including 14,702 who left military service prematurely, and 172,741 people with no record of military service, using Cox proportional hazard models, to examine the association between veteran status and length of service and cumulative risk of mental health disorder. We stratified the veterans by common lengths of service, defining Early Service Leavers as those who had served for less than 2.5 years.There were 2,794 (4.97%) first episodes of any mental health disorder in veterans, compared with 7,779 (4.50%) in nonveterans. The difference was statistically significant for all veterans (adjusted hazard ratio [HR] = 1.21; 95% CI, 1.16-1.27; P < .001). Subgroup analysis showed the highest risk to be in Early Service Leavers (adjusted HR = 1.51; 95% CI, 1.30-1.50; P < .001), including those who failed to complete initial training. The risk reduced with longer service; beyond 9 years of service, risk of mental health disorder was comparable to or lower than that in nonveterans.The veterans at highest risk of mental health disorder were those who did not complete training or minimum engagement, while those with longest service were at reduced risk, suggesting that military service was not causative. The high risk among the earliest leavers may reflect pre-service vulnerabilities not detected at recruitment, which become apparent during early training and lead to early discharge.

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