1,721,702 research outputs found
Data for: "Quantification of risk factors for herpes zoster: population based case-control study"
No full textAssociations between chronic kidney disease and age-related macular degeneration
No full textPurpose: age-related macular degeneration (AMD) and renal impairment are both associated with cardiovascular risk factors and with alterations in the complement pathways. There are few data on the association of AMD with chronic kidney disease. Methods: people who were visually impaired (binocular acuity < 6/18) due to AMD (ascertained from review of medical notes; n = 516) were compared to people with normal vision (6/6 or better; n = 2755). Cases with AMD and controls derive from a population-based cross-sectional study of people aged 75 years and over registered with 49 family practices in Britain. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease formula and proteinuria assessed by dipsticks. Results: after adjusting for a wide range of confounding factors, the presence of proteinuria was positively associated with AMD among men (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05, 4.04) but not in women (OR 0.62 95%CI 0.36,1.08). Among men, eGFR < 45 ml/min/1.73 m2 was associated with AMD but not after adjusting for proteinuria. This was not observed for women. Both proteinuria and eGFR showed different associations with AMD by sex (p-values for interaction < 0.05). Conclusions: proteinuria appears to be a risk factor for AMD among men but not among women, possibly due to measurement errors in detecting proteinuria in wome
Diabetes in the older person
Full text linkBackground.
More people are being diagnosed and treated for diabetes who are aged
over 75 years. Compared to younger diabetic populations there is less
published evidence available in the older person. At the extremes of old
age the evidence base is even smaller.
Aim.
To examine several aspects of diabetic epidemiology in the older person
in order to expand the evidence base for practice and policy.
Methods
People with diabetes were identified from a representative community
based sample of 15095 people aged at least 75 years old. Associations
between diabetes and its end points were identified. Admission to hospital
and death were assessed in an older diabetic population.
Results.
There were 1177 people identified with type 2 diabetes giving a
prevalence of 7.80% (95% Cl, 7.11-8.47). The prevalence of diabetic
complications of poor vision, proteinuria, raised creatinine, angina,
myocardial infarction, cerebrovdscular accident and foot ulceration were
all increased in the diabetic population. Older diabetic people
demonstrated a good uptake of diabetic services including regular eye
examination, annual chiropody and dietician attendance. However, the
understanding of daily diabetic management was poor with a high
prevalence of cognitive impairment (22.5%) in the diabetic population. The
rate of admission to hospital and length of hospital stay were increased in
the older diabetic person compared to the non diabetic person; rate ratio
for admission, 1.31 (95% Cl, 1.23-1.39) and the length of stay 13.9 days versus 12.4 days, p<0.001. Finally, the risk of death among people with
diabetes was higher than for people without diabetes, hazard ratio 1.50
(95% Cl, 1.38-1.65), p<0.001. The hazard ratio was similarly raised in both
men and women with diabetes across the age ranges studied.
Conclusion
This thesis presents the largest community based study in the older
diabetic person. Diabetes was shown to contribute to morbidity and
mortality until the extremes of old age
The effect on cardiovascular risk factors of migration from rural to urban areas in Peru
Full text linkDuring the 20 years of political violence in Peru starting in the late 1970’s, Ayacucho, an Andean department, was one of the most severely affected areas. Mass-migration to Lima increased largely driven by escaping from violence rather than by economic reasons. This provides a unique opportunity to study the effects of migration on health since selection biases are likely to be reduced.
This study investigates differences in cardiovascular risk factors comparing three groups: i) always lived in Ayacucho (n=289); ii) migrated from Ayacucho to Lima (n=589); and, iii) always lived in Lima (n=199). A cross sectional design was used.
A clear gradient of risk was seen for the majority of factors studied: body mass index (BMI), total and LDL-cholesterol, fasting blood glucose and insulin, CRP and fibrinogen, the rural group having the lowest risk, the urban group the highest. The migrant group had intermediate risk, although generally more similar to the urban than the rural group. Blood pressure did not show a clear gradient of difference between groups. The migrant group had similar systolic blood pressure (SBP) but lower diastolic blood pressure (DBP) than the rural group. The urban group had higher SBP but similar DBP than rural group. In the case of lipid profile, no difference was observed between groups for HDL and triglycerides. Obesity, diabetes, metabolic syndrome and estimated absolute cardiovascular risk were all higher in migrant and urban groups than in the rural sample. Within the migrant group, when classified by time since migration or age at migration, differences were observed in total cholesterol, LDL, fasting glucose and insulin resistance.
The findings of this study suggest the impact of migration on cardiovascular risk is not uniform across risk factors. The study provides new insights into the increased disease risk associated with migration and urbanisation
Use of electronic health records to investigate the role of acute inflammation and infection in vascular disease
Full text linkPrevious studies have demonstrated that acute systemic inflammation after surgery or
infection is associated with a transient increase in the risk of vascular events. This
suggests that vascular risk is not stable but fluctuates within short periods in response
to inflammatory stimuli. While an association between respiratory tract infection and
vascular events is well-documented, the effects of other acute infections and
inflammatory stimuli are less certain.
The principal aim of this project was to investigate further the role of acute
inflammation and infection in vascular disease, employing the unique opportunities
offered by electronic health record databases. Two large observational studies were
undertaken. First, the self-controlled case series method and Medicaid claims data
from the United States were used to examine the short-term effects of invasive dental
treatment, a novel acute inflammatory model, on the risk of vascular events. Second,
a matched case-control study using primary care data from the United Kingdom
General Practice Research Database investigated the role of acute maternal infection
in the development of pre-eclampsia – a vascular disorder of pregnancy.
The case series analysis of 1152 adults with a vascular event demonstrated a
transiently increased vascular event rate in the four weeks after invasive dental
treatment relative to unexposed time periods. The analysis of 1533 pre-eclampsia
cases and 14236 controls who had completed a pregnancy without pre-eclampsia
revealed an increased risk of pre-eclampsia associated with antibiotic prescriptions
and urinary infection, but not respiratory infection, during pregnancy.
The findings suggest that exposures sufficient to produce an acute inflammatory
response may play an important role in the occurrence of vascular outcomes. Future
research on the effects of other acute inflammatory triggers and the mediating
mechanisms involved should help establish a clearer role for acute inflammation and
infection in vascular disease and inform preventative strategies during periods of
increased vascular risk
Ethnic inequalities in health and use of healthcare in the UK: how computerised health records can contribute substantively to the knowledge base
Full text linkPrevious studies in the UK have established that minority ethnic groups as a whole experience more ill-health and onset of morbidity at younger ages or at lower levels of risk than the ‘White British’ population. Since the Race Relations Act of 1968, the official collection of ethnic group statistics by all government bodies has been mandated as a pre-requisite for identifying and tackling ethnic inequalities. The capture of ethnicity data in routine health records across the UK National Health Service forms part of this initiative. Although the facility to record ethnicity has been available in primary care since 1991 and in secondary care since 1995, until recently, unsystematic recording resulted in poor quality of the initial data, limiting the usefulness of these data for clinical care, commissioning and research. The incentivisation of ethnicity recording in 2006 as part of the Quality and Outcomes Framework has resulted in an improvement of the quality of these data, though their suitability for use in UK-wide population-based research, at the commencement of this PhD, had not yet been explored.
The studies reported in this thesis investigated the utility of electronic health records for research into ethnic differences in health and comprised three sub-studies. Firstly, the completeness, usability and generalisability of ethnicity data captured in primary and secondary care databases were assessed. Results showed that in 2012, valid ethnicity was recorded for 78.3% of patients in the Clinical Practice Research Datalink (CPRD), 79.4% of inpatients, and 50% of A&E patients and outpatients in the Hospital Episode Statistics for England (HES). Over 80% of patients with multiple ethnicities recorded had codes which either were identical or fell into the same five high-level ethnic group categorisation. The ethnic breakdown of the CPRD was found to be comparable to that of the combined censuses for England, Wales, Scotland and Northern Ireland, suggesting that studies of ethnic populations within the CPRD can be generalised to the UK population, particularly when using data from 2006 onwards, where completeness and consistency are highest.
Secondly, in collaboration with the UK Biobank study, a pragmatic and comprehensive definition of diabetes mellitus for use in electronic health databases was developed. Once applied to the CPRD, the algorithms identified 34,530 individuals with type 1 diabetes and 355,717 individuals with type 2 diabetes. The incidence of type 2 diabetes was almost doubled in South Asian compared with White groups (70.7 vs 42.0 events per 10,000 person years). After adjustment for gender and age group, the risk of type 2 diabetes was over three times higher in the South Asian group compared with White the group (Hazard Ratio 3.27 95%CI 3.19, 3.35).
Finally, a prospective cohort study of 860,000 patients registered with the CPRD was undertaken to quantify ethnic differences in the risk of incident coronary heart disease (CHD) and the extent to which this relationship is modified by the presence of type 2 diabetes. The presence of diabetes increased the risk of CHD by 40%, although this reduced to 22% after accounting for age, gender and deprivation (Hazard Ratio 1.22 CI95 1.20, 1.25). The excess risk associated with diabetes was markedly higher for ethnic minority groups, with an adjusted increase of 60% and 75% in South Asian and Black African/Caribbean groups respectively, compared with 28% in the White groups. Adjusted rates of CHD were consistently higher in South Asian groups and lower in Black African/Caribbean groups, with differences more pronounced amongst men than women. Ethnic differences in CHD risk were consistently more pronounced amongst patients without type 2 diabetes than in those with type 2 diabetes.
The studies have generated novel results which provide valuable information about the usability and generalisability of ethnicity data available in UK electronic health records. They have replicated findings from non-database studies of the prevalence and incidence of diabetes and extended our knowledge of the patterning of ethnic differences in heart disease outcomes. They represent the first ever use of UK routine electronic health records to answer these questions in relation to ethnicity. Together, the findings reported in this thesis provide a unique insight into the ways in which routinely recorded ethnicity data can be maximised for the purposes of epidemiological research into health inequalities across the UK
Mendelian randomisation and cardiovascular disease
Full text linkBackground and aims: Homocysteine (Hcy), C-reactive protein (CRP), and Lipoprotein-
associated phospholipase A2 (Lp-PLA2) have been associated with a high risk of cardiovascular
disease. If casual, they are expected to provide additional tools for prevention. Utilising the unique
properties of genetic variants (randomly allocated and unmodifiable), they could be used as
unconfounded proxies of environmental exposures to investigate disease aetiology, known as
Mendelian randomisation. Herein I conduct a series of Mendelian randomisation experiments to:
(i) investigate the role of Hyc in stroke; (ii) judge causality of CRP in cardiovascular disease; (iii)
investigate the validity of Lp-PLA2 as a therapeutic target in coronary heart disease (CHD) and;
(iv) describe how the integration of cis-acting variants and their cognate proteins can be used to
dissect causal pathways.
Methods: For aim (i), I conducted synthesis research of published and unpublished studies
investigating the MTHFR/C677T variant, Hcy and stroke. For aims (ii) to (iv), a series of
prospective collaborations conducting de novo genotyping for CRP and PLA2G7 genes, were
established using European-based cardiovascular genetic studies of adults.
Results: The meta-analyses of studies on MTHFR/C677T-Hcy-Stroke to 2003, showed that
subjects with the TT genotype had on average 1.93 µmol/L higher levels of Hcy compared with
subjects with CC genotype, and an odds ratio (OR) of stroke of 1.26 (95%Cl: 1.14,1.40). An
update analyses to 2008 showed that in both MTHFR-Hcy and MTHFR-stroke associations,
studies in Asia had the largest effect, followed by Europe with intermediate effect, and lower or
negligible effect in the Americas and Australasia. Analysis on CRP, indicated that subjects
homozygous for the T-allele of CRP/+1444C>T variant despite having 0.68 mg/L higher levels of
CRP, had no increase in risk of myocardial infarction (OR of 1.01 [95CI: 0.74,1.38]). A tagging-
haplotype approach showed a gradual increase on CRP levels by haplotype, but no effect on
CHID, diabetes or stroke. Analysis of the seven PLA2G7 tagging-SNPs showed that the best
variant (rs1051931) had small to moderate effects on the Lp-PLA2 activity (up to 7% relative
differences). No genetic signal with CHD was observed for any PLA2G7 variant, despite some
comparisons including up to 8412 CHID cases. A description of the proof of principle, illustrating
how to utilise cis-acting variants and their cognate proteins to distinguish causal from non-causal
effects among correlated blood proteins was presented, using as an example 6 proteins that have
been associated with CHD risk.
Conclusions: Genetic evidence reported in this document suggested that the MTHFR effect is
more pronounced in geographic regions associated with low folate intake. Genetic studies on
CRP presented in this document indicated that CRP is unlikely to be causal in cardiovascular
disease. A genetic approach using common variants in PLA2G7 had a reduced ability to confirm
or reject Lp-PLA2 as a valid drug target. Finally, integration of cis-acting variants with their
cognate proteins seems to be an effective way of dissecting biological pathways
Blood-free risk scores and neuropathy assessment tools to detect undiagnosed type 2 diabetes in Peru.
Full text linkThe prevalence of type 2 diabetes mellitus is rising, especially in low- and middle-income countries, where the situation is worsened because around half of cases are unaware of the disease. Universal screening utilizing blood markers can be challenging in resource-constrained settings. The identification of these individuals can be potentially addressed using risk scores and neuropathy assessment tools. This study aimed to assess the diagnostic accuracy of the FINDRISC, a blood-free risk score, three neuropathy assessment tools (EZSCAN, pupillometer, and biothesiometer), alone and in combination.
A population-based study was conducted enrolling a sex-stratified random sample of participants from Tumbes, a semiurban area in the north of Peru. Undiagnosed T2DM was the outcome, defined using WHO OGTT thresholds. Diagnostic accuracy of the FINDRISC and neuropathy tools was evaluated using the area under the ROC curve (aROC) and respective 95% confidence intervals (95%CI).
Data from 1609 participants were analysed, mean age 48.2 (SD: 10.6) years, 810 (50.3%) females. A total of 176 (10.9%) individuals had T2DM, and only 71 (4.7%) had undiagnosed T2DM. The diagnostic accuracy of the FINDRISC was aROC = 0.69 (95% CI: 0.64–0.74), with a sensitivity of 69% and specificity of 67%. Among devices, the EZSCAN (aROC = 0.59; 95%CI: 0.53–0.66; sensitivity of 59% and specificity of 54%) and biothesiometer in the third metatarsal head (aROC = 0.60; 95%CI: 0.53–0.67; sensitivity of 31% and specificity of 85%) performed best. A combination of the FINDRISC and the biothesiometer had the best diagnostic accuracy, with a similar aROC of FINDRISC alone (AROC = 0.69; 95%CI: 0.68–0.78), with a sensitivity of 79% and a specificity of 59%.
Our results confirm that combination of the FINDRISC and biothesiometer can improve diagnostic accuracy of the FINDRISC and biothesiometer alone, increasing sensitivity without affecting specificity or the area under the ROC curve
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