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  • Genetically Determined Levels of Circulating Cytokines and Risk of Stroke: Role of Monocyte Chemoattractant Protein-1.

    11 January 2019

    BACKGROUND: Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a two-sample Mendelian randomization (MR) study. METHODS: Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study (GWAS) of 8,293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE GWAS dataset (67,162 cases; 454,450 controls) applying inverse-variance-weighted meta-analysis, weighted-median analysis, MR-Egger regression, and multivariable MR. The UK Biobank cohort was used as an independent validation sample (4,985 cases; 364,434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits using publicly available GWAS data. RESULTS: Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (OR per 1-SD increase: 1.06, 95% CI: 1.02-1.09, p=0.0009), any ischemic stroke (OR: 1.06, 95% CI: 1.02-1.10, p=0.002), large artery stroke (OR: 1.19, 95% CI: 1.09-1.30, p=0.0002) and cardioembolic stroke (OR: 1.14, 95% CI: 1.06-1.23, p=0.0004), but not with small vessel stroke or intracerebral hemorrhage. The results were stable in sensitivity analyses and remained significant after adjustment for cardiovascular risk factors. Analyses in the UK Biobank showed similar associations for available phenotypes (any stroke: OR: 1.08, 95% CI: 0.99-1.17, p=0.09; any ischemic stroke: OR: 1.07, 95% CI: 0.97-1.18, p=0.17). Genetically determined higher MCP-1 levels were further associated with coronary artery disease (OR: 1.04, 95% CI: 1.00-1.08, p=0.04) and myocardial infarction (OR: 1.05, 95% CI: 1.01-1.09, p=0.02), but not with atrial fibrillation. A meta-analysis of observational studies showed higher circulating MCP-1 levels in stroke patients compared to controls. CONCLUSIONS: Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, particularly with large artery stroke and cardioembolic stroke. Whether targeting MCP-1 or its receptors can lower stroke incidence requires further study.

  • [Associations between family history of major chronic diseases and healthy lifestyles in Chinese adults].

    11 January 2019

    Objective: To examine the associations between family history of major chronic diseases and healthy lifestyle in adults in China. Methods: Data were from the baseline and second survey of China Kadoorie Biobank study, which were conducted during 2004-2008 and 2013-2014, respectively. After excluding participants with self-reported histories of coronary heart disease, stroke, cancer or diabetes, a total of 461 213 adults from baseline survey and 20 583 adults from second survey were included in the current study. Participants who reported a family history of acute myocardial infarction, stroke, cancer, or diabetes of any first-degree relative (i.e., biological father, mother, or siblings) were defined as having a family history of major chronic diseases. Healthy lifestyles were defined as current nonsmoking, non-excessive alcohol drinking, eating vegetables and fruits daily, upper quarter of physical activity level, body mass index (BMI) of (18.5-23.9) kg/m(2), and waist- to-hip ratio (WHR) <0.90 (man)/<0.85 (women). Results: At baseline survey, 36.5% of the participants had family history of major chronic diseases. Proportions of the above six healthy lifestyles were 70.5%, 93.0%, 18.0%, 25.0%, 53.4%, and 43.5%, respectively. Compared with participants without family history, the proportions of current nonsmoking, non-excessive drinking, normal BMI, and normal WHR were lower in participants with family history of major chronic diseases, while the proportions of eating vegetables and fruits daily, and being physically active, were higher. In general, the absolute differences in these proportions between participants with and without a family history were only slight. Similar results were observed when other family history status (the type or number of disease, the category or number of affected family members) were analysed. The association between family history of major chronic diseases and healthy lifestyles was consistently observed in the second survey 10 years later. Conclusion: In Chinese population, adults with family history of major chronic diseases did not adopt healthier lifestyles.

  • Relationship of being threatened or injured with a weapon in school with suicidal ideation and attempt among school students: a school-based study in Zhejiang Province, China.

    11 January 2019

    BACKGROUND: Suicide is the second leading cause of death among 15-29 year old youths globally, and the third most common external cause of death in China. School bullying can cause serious consequences among adolescents, including psychosocial problems, low self-esteem and post-traumatic stress disorder. Most studies examining the associations between being bullied in school and suicide are from Western, developed countries. Moreover, few studies focus on being threatened or injured with a weapon, which may cause serious body injury. Our study aimed to explore the relationship of being threatened or injured with a weapon in school with suicidal ideation and attempt among middle and high school students in Zhejiang Province, China. METHODS: A cross-sectional study of 23,543 students in grades 7-12 from 442 schools was carried out through an anonymous self-administered questionnaire between April and May 2017. Multivariable logistic regression models were used to examine the relationship of being threatened or injured with a weapon in school with suicidal ideation and attempt. RESULTS: 51.3% of participants were boys, and mean (SD) age was 15.6 (1.7) years. The overall prevalence of suicidal ideation and attempt were 16.1% (95%CI: 15.3-16.9) and 3.6% (95%CI: 3.3-4.0), respectively. Prevalence was higher among girls than boys (ideation: 19.1% vs. 13.3%. attempt: 4.4% vs. 2.9%). 13.2% of students reported being threatened or injured with a weapon in school in the past 12 months (95%CI: 11.9-14.5), higher among boys than girls (15.7% vs. 10.5%), and among rural students than urban students (13.9% vs. 11.6%). After adjustment for socio-demographic status, lifestyle factors, academic performance, self-reported health and mental health, the odds ratios for suicidal ideation and attempt among students who reported being threatened or injured with a weapon were 1.46 (1.31-1.61) and 1.68 (1.31-2.13) respectively, as compared with those who did not report being threatened or injured. CONCLUSIONS: Preventive measures for physical bullying in school need to be reinforced in China. Being threatened or injured with a weapon is associated with both suicidal ideation and attempt among middle and high school students. Suicide prevention should be an important component of psychological interventions for threatened or injured students.

  • Feasibility of Telemonitoring Blood Pressure in Patients With Kidney Disease (Oxford Heart and Renal Protection Study-1): Observational Study.

    11 January 2019

    Background: Blood pressure (BP) is a key modifiable risk factor for patients with CKD, with current guidelines recommending strict control to reduce the risk of both progression of CKD and cardiovascular disease. Trials of BP lowering require multiple visits to achieve target BP which increases the costs of such trials, and in routine care BP measured in clinic may not accurately reflect usual BP. Objective: We sought to assess whether a telemonitoring system for BP (using a Bluetooth-enable BP machine which could transmit BP measurements to a tablet device which had a bespoke app to guide measurement of BP and collect questionnaire data) was acceptable to patients with CKD, and whether patients would provide sufficient BP readings to assess variability and guide treatment. Methods: 25 participants with CKD were trained to use the telemonitoring equipment, asked to record BP daily for 30 days, attend a study visit, and then record BP on alternate days for the next 60 days. They were also offered a wrist-worn applanation tonometry device (BPro) which measures BP every 15 minutes over a 24 hour period.Participants were given questionnaires at the one-month and three-month time points, derived from the System Usability Scale and Technology Acceptance Model. All eligible participants completed the study. Results: Mean age was 58 (SD 11) years and mean eGFR was 36 (SD 13) mL/min/1.73m2. 13 out of 25 (52%) participants provided >90% of expected data and 18 out of 25 (72%) provided >80% expected data. The usability of the telemonitoring system was rated highly with mean scores of 84.9/100 (SE 2.8) after 30 days and 84.2/100 (SE 4.1) after 90 days. The coefficient of variation (CV) for variability of telemonitoring systolic BP was 9.4% (95% confidence interval [CI] 7.8 to 10.9), compared to 7.9% (95% CI 6.4-9.5) for the BPro device (P=0.05) (and 9.0% over one year in a recently completed trial with identical eligibility criteria), indicating that most variation in BP is short-term. Conclusions: Telemonitoring is acceptable to patients with CKD and provides sufficient data to inform titration of antihypertensive therapies in either a randomized trial setting (comparing different targets BPs) or routine clinical practice. Such methods could be employed in both scenarios and reduce costs currently associated with such activities.Registration ISRCTN13725286.

  • Impact of hormone replacement therapy on breast cancer

    16 October 2018

    The use of hormone replacement therapy (HRT) and its effect on women's health are contentious issues and have been for as long as HRT has been prescribed. The use of HRT for the treatment of the symptoms of menopause is widespread and well recognized. However, the exposure to exogenous hormones in postmenopausal women and the subsequent risk of cancer in general, and breast cancer in particular, have been of interest. The reproductive life of women is marked by menarche at puberty and menopause in middle age. The definition of menopause is the cessation of menstruation as a result of ovarian failure and signifies the end of a woman's reproductive life. Ovarian failure in turn leads to decreasing circulating levels of estrogen, and the result of which is the manifestation of the acute symptoms of the menopause. These symptoms most commonly include bleeding irregularities, vasomotor, and urogenital symptoms (Critchley et al. 2005a). © 2010 Springer-Verlag London.

  • Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: cohort study.

    16 October 2018

    To determine cancer morbidity in members of the armed forces who took part in tests of chemical warfare agents from 1941 to 1989. Historical cohort study, with cohort members followed up to December 2004. Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. All veterans included in the cohort study of mortality, excluding those known to have died or been lost to follow-up before 1 January 1971 when the UK cancer registration system commenced: 17,013 male members of the UK armed forces who took part in tests (Porton Down veterans) and a similar group of 16,520 men who did not (non-Porton Down veterans). Cancer morbidity in each group of veterans; rate ratios, with 95% confidence intervals, adjusted for age group and calendar period. 3457 cancers were reported in the Porton Down veterans compared with 3380 cancers in the non-Porton Down veterans. While overall cancer morbidity was the same in both groups (rate ratio 1.00, 95% confidence interval 0.95 to 1.05), Porton Down veterans had higher rates of ill defined malignant neoplasms (1.12, 1.02 to 1.22), in situ neoplasms (1.45, 1.06 to 2.00), and those of uncertain or unknown behaviour (1.32, 1.01 to 1.73). Overall cancer morbidity in Porton Down veterans was no different from that in non-Porton Down veterans.

  • Cholesterol

    21 June 2016

    Blood lipids are a major cause of cardiovascular disease (CVD). Higher levels of LDL cholesterol and lower levels of HDL cholesterol are associated with higher heart disease risk. While this has been known for some time, it is only in recent decades that effective treatments to substantially lower LDL cholesterol have become available.

  • Smoking

    21 June 2016

    The link between smoking and lung cancer was originally discovered by Sir Richard Doll in 1956. Co-director Sir Richard Peto has continued to study the impact of tobacco of global health (see video below). Smoking cigarettes is a leading cause of premature death worldwide. There were about 100 million deaths from tobacco in the 20th century, most in developed countries. If current smoking patterns persist, it is estimated that tobacco will kill about 1 billion people this century, mostly in low- and middle-income countries, and about half of these deaths will occur before age 70.

  • Diabetes Mellitus

    21 June 2016

    Diabetes Mellitus is a group of metabolic disorders in which there are high blood sugars over a prolonged period. Rates of type-2 (or adult onset) diabetes have increased rapidly in recent decades due to changes in diet and other lifestyle factors. Patients with diabetes are at increased risk of a number of diseases, most notably cardiovascular disease, kidney disease and damage to the eyes.

  • Other Chronic Diseases

    21 June 2016

    Chronic disease is responsible for a major part of our society’s burden of disability. In addition to our research into chronic diseases such as cancer, cardiovascular disease, diabetes and renal disease we conduct a range of research into other diseases, as well as into the care of people with chronic conditions.