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1.  Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE) 
Diabetologia  2014;58:474-484.
Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children.
In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school.
Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers.
Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-014-3474-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC4320299  PMID: 25520157
Birthweight; Cardiovascular disease; Childhood; Ethnicity; Type 2 diabetes
2.  Numbers are not the whole story: a qualitative exploration of barriers and facilitators to increased physical activity in a primary care based walking intervention 
BMC Public Health  2014;14:1272.
The majority of mid-life and older adults in the UK are not achieving recommended physical activity levels and inactivity is associated with many health problems. Walking is a safe, appropriate exercise. The PACE-UP trial sought to increase walking through the structured use of a pedometer and handbook, with and without support from a practice nurse trained in behaviour change techniques (BCTs). Understanding barriers and facilitators to engagement with a primary care based physical activity intervention is essential for future trials and programmes.
We conducted semi-structured telephone interviews using a topic guide with purposive samples of participants who did and did not increase their walking from both intervention groups. Interviews were audio-recorded, transcribed and coded independently by researchers prior to performing a thematic analysis. Responsiveness to the specific BCTs used was also analysed.
Forty-three trial participants were interviewed in early 2014. Almost all felt they had benefitted, irrespective of their change in step-count, and that primary care was an appropriate setting.
Important facilitators included a desire for a healthy lifestyle, improved physical health, enjoyment of walking in the local environment, having a flexible routine allowing for an increase in walking, appropriate self and external monitoring and support from others.
Important barriers included physical health problems, an inflexible routine, work and other commitments, the weather and a mistrust of the monitoring equipment.
BCTs that were reported to have the most impact included: providing information about behaviour-health link; prompting self-monitoring and review of goals and outcomes; providing feedback; providing specific information about how to increase walking; planning social support/change; and relapse prevention. Rewards were unhelpful.
Despite our expectation that there would be a difference between the experiences of those who did and did not objectively increase their walking, we found that most participants considered themselves to have succeeded in the trial and benefitted from taking part. Barriers and facilitators were similar across demographic groups and trial outcomes. Findings indicated several BCTs on which PA trial and programme planners could focus efforts with the expectation of greatest impact as well as strong support for primary care as an appropriate venue.
Trial registration
PMCID: PMC4320609  PMID: 25511452
Qualitative research; Physical activity; Pedometer intervention; Walking; Primary care; Older adults
3.  Adiposity in Early, Middle and Later Adult Life and Cardiometabolic Risk Markers in Later Life; Findings from the British Regional Heart Study 
PLoS ONE  2014;9(12):e114289.
Objectives: This research investigates the associations between body mass index (BMI) at 21, 40–59, 60–79 years of age on cardiometabolic risk markers at 60–79 years.
Methods: A prospective study of 3464 British men with BMI measured at 40–59 and 60–79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model.
Results: At ages 21, 40–59 and 60–79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60–79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60–79 years and serum insulin, blood glucose and HbA1c at 60–79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60–79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40–59 years were mainly consistent with those of BMI at 60–79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified.
Conclusions: In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk.
PMCID: PMC4256406  PMID: 25474626
4.  Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with l-ascorbic acid1234 
Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation.
Objectives: We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations.
Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737).
Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected.
Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.
PMCID: PMC4266888  PMID: 25527764
l-ascorbic acid; cardiometabolic traits; confounding; genetic variants; reverse causation
5.  Regular Breakfast Consumption and Type 2 Diabetes Risk Markers in 9- to 10-Year-Old Children in the Child Heart and Health Study in England (CHASE): A Cross-Sectional Analysis 
PLoS Medicine  2014;11(9):e1001703.
Angela Donin and colleagues evaluated the association between breakfast consumption and composition and risk markers for diabetes and cardiovascular disease in 9- and 10-year-olds.
Please see later in the article for the Editors' Summary
Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children.
Methods and Findings
We conducted a cross-sectional study of 4,116 UK primary school children aged 9–10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%–37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%–37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%–2.0%), glucose (percent difference 1.0%, 95% CI 0.0%–2.0%), and urate (percent difference 6%, 95% CI 3%–10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers.
Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, more than 380 million people have diabetes, a disorder that is characterized by high levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone released by the pancreas after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest type of diabetes) blood sugar control fails because the fat and muscle cells that normally respond to insulin become insulin resistant. Type 2 diabetes can often be controlled initially with diet and exercise and with drugs such as metformin and sulfonylureas. However, many patients eventually need insulin injections to control their blood sugar levels. Long-term complications of diabetes, which include an increased risk of heart disease and stroke (cardiovascular disease), reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes. Risk factors for the condition include being over 40 years old and being overweight or obese.
Why Was This Study Done?
Experts predict that by 2035 nearly 600 million people will have diabetes so better strategies to prevent diabetes are urgently needed. Eating breakfast regularly—particularly a high fiber, cereal-based breakfast—has been associated with a reduced risk of type 2 diabetes (and a reduced risk of being overweight or obese) in adults. However, little is known about whether breakfast eating habits affect markers of type 2 diabetes risk in children. In this cross-sectional study (an observational investigation that studies a group of individuals at a single time point), the researchers examine the associations between breakfast consumption (both frequency and content) and risk markers for type 2 diabetes, particularly insulin resistance and glycemia (the presence of sugar in the blood), in an ethnically mixed population of children; insulin resistance and glycemia measurements in children provide important information about diabetes development later in life.
What Did the Researchers Do and Find?
The researchers invited 9–10 year old children attending 200 schools in London, Birmingham, and Leicester to participate in the Child Heart and Health Study in England (CHASE), a study examining risk factors for cardiovascular disease and type 2 diabetes in children of South Asian, black African-Caribbean, and white European origin. The researchers measured the body composition of the study participants and the levels of insulin, glucose, and other markers of diabetes risk in fasting blood samples (blood taken from the children 8–10 hours after their last meal or drink). All the participants (4,116 children) reported how often they ate breakfast; 2,004 children also completed a 24-hour dietary recall questionnaire. Seventy-four percent of the children reported that they ate breakfast every day, 11% and 9% reported that they ate breakfast most days and some days, respectively, whereas 6% reported that they rarely ate breakfast. Children who ate breakfast infrequently had higher fasting insulin levels and higher insulin resistance than children who ate breakfast every day. Moreover, the children who ate a high fiber, cereal-based breakfast had lower insulin resistance than children who ate other types of breakfast such as low fiber or toast-based breakfasts.
What Do These Findings Mean?
These findings indicate that children who ate breakfast every day, particularly those who ate a high fiber breakfast, had lower levels of risk markers for type 2 diabetes than children who rarely ate breakfast. Importantly, the association between eating breakfast and having a favorable type 2 diabetes risk profile remained after allowing for differences in socioeconomic status, physical activity levels, and amount of body fat (adiposity); in observational studies, it is important to allow for the possibility that individuals who share a measured characteristic and a health outcome also share another characteristic (a confounder) that is actually responsible for the outcome. Although trials are needed to establish whether altering the breakfast habits of children can alter their risk of developing type 2 diabetes, these findings are encouraging. Specifically, they suggest that if all the children in England who do not eat breakfast daily could be encouraged to do so, it might reduce population-wide fasting insulin levels by about 4%. Moreover, encouraging children to eat a high fiber breakfast instead of a low fiber breakfast might reduce population-wide fasting insulin levels by 11%–12%. Thus, persuading children to eat a high fiber breakfast regularly could be an important component in diabetes preventative strategies in England and potentially worldwide.
Additional Information
Please access these websites via the online version of this summary at
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including detailed information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and about living with diabetes; it also provides people's stories about diabetes; Change4Life, a UK campaign that provides tips for healthy living, has a webpage about the importance of a healthy breakfast
The charity Diabetes UK provides detailed information for patients and carers in several languages, including information on healthy lifestyles for people with diabetes
The UK-based non-profit organization Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention (in English and Spanish)
Kidshealth, a US-based not-for-profit organization provides information for parents about the importance of breakfast and information for children
More information about the Child Heart and Health Study in England (CHASE) is available
PMCID: PMC4151989  PMID: 25181492
6.  Influence of Adiposity on Insulin Resistance and Glycemia Markers Among U.K. Children of South Asian, Black African-Caribbean, and White European Origin 
Diabetes Care  2013;36(6):1712-1719.
Ethnic differences in type 2 diabetes risk between South Asians and white Europeans originate before adult life and are not fully explained by higher adiposity levels in South Asians. Although metabolic sensitivity to adiposity may differ between ethnic groups, this has been little studied in childhood. We have therefore examined the associations among adiposity, insulin resistance, and glycemia markers in children of different ethnic origins.
Cross-sectional study of 4,633 9- to 10-year-old children (response rate 68%) predominantly of South Asian, black African-Caribbean, and white European origin (n = 1,266, 1,176, and 1,109, respectively) who had homeostasis model assessments of insulin resistance (HOMA-IR), glycemia markers (HbA1c and fasting glucose), and adiposity (BMI, waist circumference, skinfold thicknesses, and bioimpedance [fat mass]).
All adiposity measures were positively associated with HOMA-IR in all ethnic groups, but associations were stronger among South Asians compared to black African-Caribbeans and white Europeans. For a 1-SD increase in fat mass percentage, percentage differences in HOMA-IR were 37.5% (95% CI 33.3–41.7), 29.7% (25.8–33.8), and 27.0% (22.9–31.2), respectively (P interaction < 0.001). All adiposity markers were positively associated with HbA1c in South Asians and black African-Caribbeans but not in white Europeans; for a 1-SD increase in fat mass percentage, percentage differences in HbA1c were 0.04% (95% CI 0.03–0.06), 0.04% (0.02–0.05), and 0.02% (−0.00 to 0.04), respectively (P interaction < 0.001). Patterns for fasting glucose were less consistent.
South Asian children are more metabolically sensitive to adiposity. Early prevention or treatment of childhood obesity may be critical for type 2 diabetes prevention, especially in South Asians.
PMCID: PMC3661837  PMID: 23315600
7.  Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach 
BMC Geriatrics  2014;14:46.
Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants.
Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation.
Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration.
Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.
PMCID: PMC3991893  PMID: 24725730
Physical activity; Non-participation; Primary care; Older people; Recruitment
Diabetes care  2013;37(1):116-123.
Energy intake, energy density and nutrient intakes are implicated in type 2 diabetes risk in adults, but little is known about their influence on emerging type 2 diabetes risk in childhood. We examined these associations in a multi-ethnic population of children.
Research Design and Methods
Cross-sectional study of 2017 children predominantly of white European, South Asian and black African-Caribbean origin aged 9-10 years who had a detailed 24 hour dietary recall, measurements of body composition and provided a fasting blood sample for measurements of plasma glucose, HbA1c and serum insulin; HOMA insulin resistance was also derived.
Energy intake was positively associated with insulin resistance. After the removal of 176 participants with implausible energy intakes (unlikely to be representative of habitual intake), energy intake was more strongly associated with insulin resistance, and was also associated with glucose and fat mass index. Energy density was also positively associated with insulin resistance and fat mass index. However, in mutually adjusted analyses, the associations for energy intake remained while those for energy density became non-significant. Individual nutrient intakes showed no associations with type 2 diabetes risk markers.
Higher total energy intake was strongly associated with high levels of insulin resistance and may help to explain emerging type 2 diabetes risk in childhood. Studies are needed to establish whether reducing energy intake produces sustained favourable changes in insulin resistance and circulating glucose levels.
PMCID: PMC3966263  PMID: 23939542
9.  Spurious trends in coronary heart disease incidence: unintended consequences of the new GP contract? 
Comparisons of the same patient data in 2004 and 2006 downloads of the DIN-LINK UK primary care database demonstrated unexpected differences in the rates of coronary heart disease between the datasets. Incidence rates were lower between 1996–2003 in the new (2006) download. Patient record checks demonstrated that coronary heart disease codes had been removed in the new download during the run-up to the new contract. Planners need to be aware of such issues when evaluating trends in CHD or other similar conditions.
PMCID: PMC2078192  PMID: 17550675
coronary heart disease; electronic patient records; primary care database; quality and outcomes framework
10.  PACE-UP (Pedometer and consultation evaluation - UP) – a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45–75 years: study protocol for a randomised controlled trial 
Trials  2013;14:418.
Most adults do not achieve the 150 minutes weekly of at least moderate intensity activity recommended for health. Adults’ most common physical activity (PA) is walking, light intensity if strolling, moderate if brisker. Pedometers can increase walking; however, most trials have been short-term, have combined pedometer and support effects, and have not reported PA intensity. This trial will investigate whether pedometers, with or without nurse support, can help less active 45–75 year olds to increase their PA over 12 months.
Design: Primary care-based 3-arm randomized controlled trial with 12-month follow-up and health economic and qualitative evaluations.
Participants: Less active 45–75 year olds (n = 993) will be recruited by post from six South West London general practices, maximum of two per household and households randomised into three groups. Step-count and time spent at different PA intensities will be assessed for 7 days at baseline, 3 and 12 months by accelerometer. Questionnaires and anthropometric assessments will be completed.
Intervention: The pedometer-alone group will be posted a pedometer (Yamax Digi-Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking programme, using targets from their baseline assessment. The pedometer-plus-support group will additionally receive three practice nurse PA consultations. The handbook, diary and consultations include behaviour change techniques (e.g., self-monitoring, goal-setting, relapse prevention planning). The control group will receive usual care.
Outcomes: Changes in average daily step-count (primary outcome), time spent sedentary and in at least moderate intensity PA weekly at 12 months, measured by accelerometry. Other outcomes include change in body mass index, body fat, self-reported PA, quality of life, mood and adverse events. Cost-effectiveness will be assessed by the incremental cost of the intervention to the National Health Service and incremental cost per change in step-count and per quality adjusted life year. Qualitative evaluations will explore reasons for trial non-participation and the interventions’ acceptability.
The PACE-UP trial will determine the effectiveness and cost-effectiveness of a pedometer-based walking intervention delivered by post or practice nurse to less active primary care patients aged 45–75 years old. Approaches to minimise bias and challenges anticipated in delivery will be discussed.
Trial registration
PMCID: PMC4235020  PMID: 24304838
Accelerometers; Behaviour change techniques; Cognitive behavioural; Middle-aged adults; Older people; Pedometers; Physical activity; Postal; Practice nurse; Primary care; Walking intervention
11.  Mortality Associations with Long-Term Exposure to Outdoor Air Pollution in a National English Cohort 
Rationale: Cohort evidence linking long-term exposure to outdoor particulate air pollution and mortality has come largely from the United States. There is relatively little evidence from nationally representative cohorts in other countries.
Objectives: To investigate the relationship between long-term exposure to a range of pollutants and causes of death in a national English cohort.
Methods: A total of 835,607 patients aged 40–89 years registered with 205 general practices were followed from 2003–2007. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter less than 10 (PM10) and less than 2.5 μm (PM2.5), nitrogen dioxide (NO2), ozone, and sulfur dioxide (SO2) at 1 km2 resolution, estimated from emission-based models, were linked to residential postcode. Deaths (n = 83,103) were ascertained from linkage to death certificates, and hazard ratios (HRs) for all- and cause-specific mortality for pollutants were estimated for interquartile pollutant changes from Cox models adjusting for age, sex, smoking, body mass index, and area-level socioeconomic status markers.
Measurements and Main Results: Residential concentrations of all pollutants except ozone were positively associated with all-cause mortality (HR, 1.02, 1.03, and 1.04 for PM2.5, NO2, and SO2, respectively). Associations for PM2.5, NO2, and SO2 were larger for respiratory deaths (HR, 1.09 each) and lung cancer (HR, 1.02, 1.06, and 1.05) but nearer unity for cardiovascular deaths (1.00, 1.00, and 1.04).
Conclusions: These results strengthen the evidence linking long-term ambient air pollution exposure to increased all-cause mortality. However, the stronger associations with respiratory mortality are not consistent with most US studies in which associations with cardiovascular causes of death tend to predominate.
PMCID: PMC3734610  PMID: 23590261
air pollution; mortality; cohort study; respiratory
12.  Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study 
PLoS ONE  2013;8(11):e77734.
Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement.
To describe initiation of psychotropic medication in the first year after partner bereavement.
In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls.
The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement.
Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use.
PMCID: PMC3818377  PMID: 24223722
13.  Are Ethnic and Gender Specific Equations Needed to Derive Fat Free Mass from Bioelectrical Impedance in Children of South Asian, Black African-Caribbean and White European Origin? Results of the Assessment of Body Composition in Children Study 
PLoS ONE  2013;8(10):e76426.
Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat.
Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}.
Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set.
Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences.
PMCID: PMC3799736  PMID: 24204625
14.  Quality of prescribing in care homes and the community in England and Wales 
The British Journal of General Practice  2012;62(598):e329-e336.
Care home residents are vulnerable to the adverse effects of prescribing but there is limited monitoring in the UK.
To compare prescribing quality in care homes in England and Wales with the community and with US nursing homes.
Design and setting
Cross-sectional analysis of a UK primary care database and comparison with the US National Nursing Home Survey including 326 general practices in 2008–2009 in England and Wales, with 10 387 care home and 403 259 community residents aged 65 to 104 years.
Comparison of age- and sex-standardised use of ‘concern’ and common drug groups in the last 90 days and potentially inappropriate prescribing based on a consensus list of medications best avoided in older people (Beers criteria).
Compared to the community, care home residents were more likely to receive ‘concern’ drugs, including benzodiazepines (relative risk (RR) = 2.05, 95% confidence interval (CI) = 1.90 to 2.22), anticholinergic antihistamines (RR = 2.78, 95% CI = 2.38 to 3.23), loop diuretics (RR = 1.47, 95% CI = 1.41 to 1.53), and antipsychotics (RR = 22.7, 95% CI = 20.6 to 24.9). Use of several common drug groups, including laxatives, antidepressants, and antibiotics, was higher, but use of cardiovascular medication was lower. Thirty-three per cent (95% CI = 31.7% to 34.3%) of care home residents in England and Wales received potentially inappropriate medication, compared to 21.4% (95% CI = 20.9% to 21.8%) in the community. The potentially inappropriate prescribing rate in US nursing homes was similar to England and Wales.
Care home prescribing has the potential for improvement. High use of anticholinergic and psychotropic medication may contribute to functional and cognitive decline. The targeting and effectiveness of medication reviews in care homes needs to be improved.
PMCID: PMC3338054  PMID: 22546592
community; inappropriate prescribing; nursing homes; prescribing patterns; primary care
15.  Genetic variation at the SLC23A1 locus is associated with circulating levels of L-ascorbic acid (Vitamin C). Evidence from 5 independent studies with over 15000 participants 
L-ascorbic acid is an essential part of the human diet and has been associated with a wide-range of chronic complex diseases including cardiovascular outcomes. To date, there are no confirmed genetic correlates of circulating levels of L-ascorbic acid.
We aimed to confirm the existence of association between common variation at the SLC23A1 gene locus and circulating levels of L-ascorbic acid.
We employed a two-stage design which used a discovery cohort (the British Women’s Heart and Health Study) and a series of follow-up cohorts and meta-analysis (totalling 15087 participants) to assess the relationship between variation at SLC23A1 and circulating levels of L-ascorbic acid.
In the discovery cohort, variation at rs33972313 was associated with a reduction in circulating levels of L-ascorbic acid (−4.15μmol/L (95%CI −0.49, −7.81), p=0.03 reduction per minor allele). Pooled analysis of the relationship between rs33972313 and circulating L-ascorbic acid across all studies confirmed this, showing that each additional rare allele was associated with a reduction in circulating levels of L-ascorbic acid of −5.98μmol/L (95%CI −8.23, −3.73), p=2.0×10−7 per minor allele.
Work here has identified a genetic variant (rs33972313) in the SLC23A1 vitamin C active transporter locus that is reliably associated with circulating levels of L-ascorbic acid in the general population. This finding has implications more generally for the epidemiological investigation of relationships between circulating L-ascorbic acid and health outcomes.
PMCID: PMC3605792  PMID: 20519558
Vitamin C; genotype; L-ascorbic acid
16.  Do Good Health and Material Circumstances Protect Older People From the Increased Risk of Death After Bereavement? 
American Journal of Epidemiology  2012;176(8):689-698.
An increased risk of death in persons who have suffered spousal bereavement has been described in many populations. The impact of modifying factors, such as chronic disease and material circumstances, is less well understood. The authors followed 171,120 couples 60 years of age or older in a United Kingdom primary care database between 2005 and 2010 for an average of 4 years. A total of 26,646 (15.5%) couples experienced bereavement, with mean follow up after bereavement of 2 years. In a model adjusted for age, sex, comorbid conditions at baseline, material deprivation based on area of residence, season, and smoking status, the hazard ratio for mortality in the first year after bereavement was 1.25 (95% confidence interval: 1.18, 1.33). Further adjustment for changes in comorbid conditions throughout follow up did not alter the hazard ratio for bereavement (hazard ratio = 1.27, 95% confidence interval: 1.19, 1.35). The association was strongest in individuals with no significant chronic comorbid conditions throughout follow up (hazard ratio = 1.50, 95% confidence interval: 1.28, 1.77) and in more affluent couples (P = 0.035). In the first year after bereavement, the association between bereavement and death is not primarily mediated through worsening or new onset of chronic disease. Good health and material circumstances do not protect individuals from increased mortality rates after bereavement.
PMCID: PMC3472615  PMID: 23051600
aged; bereavement; comorbid conditions; mortality
17.  Family dog ownership and levels of physical activity in childhood: findings from the Child Heart And health Study in England (CHASE) 
American journal of public health  2010;100(9):1669-1671.
Dog ownership is associated with higher levels of physical activity in adults; whether this association occurs in children is unknown. We examined objectively assessed levels of physical activity (using accelerometry) in 2065 children aged 9-10 years. Children from dog-owning families spent more time in light, moderate-vigorous physical activity, and recorded higher levels of activity counts-per-minute (25, 95%CI 6-44), and steps (357, 95%CI 14-701) per day than those who did not. Children living with pet-dogs are slightly more active, though the precise reasons have still to be established.
PMCID: PMC2920992  PMID: 20634441
Dog ownership; physical activity; children
18.  Cardiometabolic Risk Markers in Indian Children: Comparison with UK Indian and White European Children 
PLoS ONE  2012;7(4):e36236.
UK Indian adults have higher risks of coronary heart disease and type 2 diabetes than Indian and UK European adults. With growing evidence that these diseases originate in early life, we compared cardiometabolic risk markers in Indian, UK Indian and white European children.
Comparisons were based on the Mysore Parthenon Birth Cohort Study (MPBCS), India and the Child Heart Health Study in England (CHASE), which studied 9–10 year-old children (538 Indian, 483 UK Indian, 1375 white European) using similar methods. Analyses adjusted for study differences in age and sex.
Compared with Mysore Indians, UK Indians had markedly higher BMI (% difference 21%, 95%CI 18 to 24%), skinfold thickness (% difference 34%, 95%CI 26 to 42%), LDL-cholesterol (mean difference 0.48, 95%CI 0.38 to 0.57 mmol/L), systolic BP (mean difference 10.3, 95% CI 8.9 to 11.8 mmHg) and fasting insulin (% difference 145%, 95%CI 124 to 168%). These differences (similar in both sexes and little affected by adiposity adjustment) were larger than those between UK Indians and white Europeans. Compared with white Europeans, UK Indians had higher skinfold thickness (% difference 6.0%, 95%CI 1.5 to 10.7%), fasting insulin (% difference 31%, 95%CI 22 to 40%), triglyceride (% difference 13%, 95%CI 8 to 18%) and LDL-cholesterol (mean difference 0.12 mmol/L, 95%CI 0.04 to 0.19 mmol/L).
UK Indian children have an adverse cardiometabolic risk profile, especially compared to Indian children. These differences, not simply reflecting greater adiposity, emphasize the need for prevention strategies starting in childhood or earlier.
PMCID: PMC3338673  PMID: 22558399
19.  Socio-Economic Position and Type 2 Diabetes Risk Factors: Patterns in UK Children of South Asian, Black African-Caribbean and White European Origin 
PLoS ONE  2012;7(3):e32619.
Socio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors.
Methods and Findings
Cross-sectional school-based study of 4,804 UK children aged 9–10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (−1.12%; [−2.01, −0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups.
SEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce emerging ethnic differences in T2DM risk.
PMCID: PMC3296720  PMID: 22412897
20.  The estimated prevalence and incidence of late stage age related macular degeneration in the UK 
UK estimates of age related macular degeneration (AMD) occurrence vary.
To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years.
Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007–2009 population data. Incidence was estimated from modelled age-specific prevalence.
Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year.
These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments.
PMCID: PMC3329633  PMID: 22329913
Prevalence; incidence; AMD; UK; epidemiology; clinical trial
21.  Travel to School and Physical Activity Levels in 9–10 Year-Old UK Children of Different Ethnic Origin; Child Heart and Health Study in England (CHASE) 
PLoS ONE  2012;7(2):e30932.
Travel to school may offer a convenient way to increase physical activity levels in childhood. We examined the association between method of travel to school and physical activity levels in urban multi-ethnic children.
Methods and Findings
2035 children (aged 9–10 years in 2006–7) provided data on their usual method of travel to school and wore an Actigraph-GT1M activity monitor during waking hours. Associations between method of travel and mean level of physical activity (counts per minute [CPM], steps, time spent in light, moderate or vigorous activity per day) were examined in models adjusted for confounding variables. 1393 children (69%) walked or cycled to school; 161 (8%) used public transport and 481 (24%) travelled by car. White European children were more likely to walk/cycle, black African Caribbeans to travel by public transport and South Asian children to travel by car. Children travelling by car spent less time in moderate to vigorous physical activity (−7 mins, 95%CI-9,-5), and had lower CPM (−32 CPM, 95%CI-44,-19) and steps per day (−813 steps, 95%CI,-1043,-582) than walkers/cyclists. Pupils travelling by public transport had similar activity levels to walkers/cyclists. Lower physical activity levels amongst car travellers' were especially marked at travelling times (school days between 8–9 am, 3–5 pm), but were also evident on weekdays at other times and at weekends; they did not differ by gender or ethnic group.
Active travel to school is associated with higher levels of objectively measured physical activity, particularly during periods of travel but also at other times. If children travelling by car were to achieve physical activity levels (steps) similar to children using active travel, they would increase their physical activity levels by 9%. However, the population increase would be a modest 2%, because of the low proportion of car travellers in this urban population.
PMCID: PMC3272007  PMID: 22319596
22.  Depression indicators in a national sample of older community and care home patients: applying the Quality and Outcomes Framework 
In a national primary care database sample of older people (≥65 years), 81% (83 588/103 821) of community and 58% (1702/2940) of care home residents with diabetes or heart disease had depression case finding recently recorded; 66% (1418/2145) of community and 22% (26/118) of care home residents with a new depression episode had a depression-severity assessment recorded. Age, sex, and higher care home dementia prevalence did not explain these differences. Case finding and assessment of depression need to be improved in older people, particularly care home residents.
PMCID: PMC3026153  PMID: 21276341
depression; homes for the aged; elderly; quality indicators, health care
23.  Patterns of body size and adiposity among UK children of South Asian, black African–Caribbean and white European origin: Child Heart And health Study in England (CHASE Study) 
Background The objective of this study was to examine adiposity patterns in UK South Asian, black African–Caribbean and white European children using a range of adiposity markers. A cross-sectional survey in London, Birmingham and Leicester primary schools was conducted. Weight, height, waist circumference, skinfold thickness values (biceps, triceps, subscapular and suprailiac) were measured. Fat mass was derived from bioimpedance; optimally height-standardized indices were derived for all adiposity markers. Ethnic origin was based on parental self-report. Multilevel models were used to obtain adjusted means and ethnic differences adjusted for gender, age, month, observer and school (fitted as a random effect). A total of 5887 children aged 9–10 years participated (response rate 68%), including 1345 white Europeans, 1523 South Asians and 1570 black African–Caribbeans.
Results Compared with white Europeans, South Asians had a higher sum of all skinfolds and fat mass percentage, and their body mass index (BMI) was lower. South Asians were slightly shorter but use of optimally height-standardized indices did not materially affect these comparisons. At any given fat mass, BMI was lower in South Asians than white Europeans. In similar comparisons, black African–Caribbeans had a lower sum of all skinfolds but a higher fat mass percentage, and their BMI was higher. Black African–Caribbeans were markedly taller. Use of optimally height-standardized indices yielded markedly different findings; sum of skinfolds index was markedly lower, whereas fat mass index and weight-for-height index were similar. At any given fat mass, BMI was similar in black African–Caribbeans and white Europeans.
Conclusions UK South Asian children have higher adiposity levels and black African–Caribbeans have similar or lower adiposity levels when compared with white Europeans. However, these differences are not well represented by comparisons based on BMI, which systematically underestimates adiposity in South Asians, and in black African–Caribbeans it overestimates adiposity because of its association with height.
PMCID: PMC3043281  PMID: 21044977
Ethnicity; South Asian; African–Caribbean; adiposity; obesity; body mass index
24.  Retinal arteriolar tortuosity and cardiovascular risk factors in a multi-ethnic population study of 10 year old children; the Child Heart And health Study in England (CHASE) 
To examine the association between cardiovascular risk factors and retinal arteriolar tortuosity in a multiethnic child-population.
Cross sectional study of 986 UK primary-school children of South Asian, black African Caribbean, and white European origin aged 10-11 years. Anthropometric measurements and retinal imaging, were carried out and a fasting blood sample collected. Digital images of retinal arterioles were analysed using a validated semi-automated measure of tortuosity. Associations between tortuosity and cardiometabolic risk factors were analysed using multilevel linear regression, adjusted for gender, age, ethnicity, arteriole branch status, month and school.
Levels of arteriolar tortuosity were similar in boys and girls, and in different ethnic groups. Retinal arteriolar tortuosity was positively associated with levels of triglyceride, total and LDL cholesterol, systolic and diastolic blood pressure. One standard deviation increases in these risk factors were associated with 3.7% (95% CI 1.2, 6.4%), 3.3% (0.9, 5.8%), 3.1% (0.6, 5.6%), 2.0% (−0.3, 4.2%) and 2.3% (0.1, 4.6%) increases in tortuosity respectively. Adiposity, insulin resistance and blood glucose showed no associations with tortuosity.
Established cardiovascular risk factors, strongly linked to coronary heart disease in adulthood, may influence retinal arteriolar tortuosity at the end of the first decade of life.
PMCID: PMC3145146  PMID: 21659645
Retina; arteriolar tortuosity; cardiovascular risk
25.  Ethnic Differences in the Prevalence of Myopia and Ocular Biometry in 10- and 11-Year-Old Children: The Child Heart and Health Study in England (CHASE) 
In children from similar sociodemographic backgrounds attending the same schools, South Asian children were nine times more likely to be myopic and black African Caribbeans three times more likely, compared with white Europeans. Ethnic differences in environmental susceptibility to myopia may be explained by genetics or early life exposures.
Ethnic differences in childhood prevalence of myopia have not been well characterized in the United Kingdom. In this study, ethnic differences in refractive status and ocular biometry were examined in a multiethnic sample of British children.
This was a cross-sectional study of 10- and 11-year-old school children of South Asian, black African Caribbean, and white European ethnic origin. Vision, open-field autorefraction (without cycloplegia), and ocular biometry were measured in each eye. Myopia was defined as spherical equivalent refraction of −0.50 D with unaided vision of 20/30 or worse (in one or both eyes). Ethnic differences in the prevalence of myopia were examined by using logistic regression, and multiple linear regression was used for ethnic differences in ocular biometry. All models were adjusted for age, sex, and clustering within school.
Data were available for 1179 children. The prevalence of myopia was 25.2%, 10.0%, and 3.4%, respectively, in the South Asian, black African Caribbean, and white European children. Adjusted odds ratios (ORs) of myopia compared with the white European children were 8.9 (95% confidence interval [CI] 4.0 to 19.4) in the South Asian and 3.2 (95% CI, 1.4 to 7.2) in black African Caribbean children. Ethnic differences in the prevalence of myopia were largely accounted for by ethnic differences in axial length. The South Asian and black African Caribbean children had longer axial lengths (0.44 mm; 95% CI, 0.30 to 0.57 mm and 0.30 mm; 95% CI, 0.16 to 0.44 mm, respectively).
Among British children exposed to the same schooling environment, the South Asians had the highest prevalence of myopia, followed by the black African Caribbeans compared with the white Europeans. A quarter of British South Asian children were myopic, which is strongly related to increased axial length.
PMCID: PMC3055754  PMID: 20631242

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