Liam Smeeth

London School of Hygiene and Tropical Medicine, Londinium, England, United Kingdom

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Publications (249)1483.91 Total impact

  • Krishnan Bhaskaran, Liam Smeeth
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    ABSTRACT: The terminology describing missingness mechanisms is confusing. In particular the meaning of 'missing at random' is often misunderstood, leading researchers faced with missing data problems away from multiple imputation, a method with considerable advantages. The purpose of this article is to clarify how 'missing at random' differs from 'missing completely at random' via an imagined dialogue between a clinical researcher and statistician.
    International Journal of Epidemiology 04/2014; · 6.98 Impact Factor
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    ABSTRACT: Background. Herpes zoster is common and vaccine preventable. Stroke risk may be increased following zoster, but evidence is sparse and could be explained by differences between people with and without zoster. Our objective was to determine if stroke risk is increased following zoster. Methods. Within-person comparisons were undertaken using the self-controlled case-series method and data from the UK Clinical Practice Research Datalink (1987-2012). Participants had a first-ever diagnosis of zoster and stroke within the study period. Stroke incidence in periods following zoster was compared with incidence in other time periods. Age-adjusted incidence ratios (IRs) and 95% confidence intervals (CIs) were calculated. Results. A total of 6584 individuals were included. Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1-4 (age-adjusted IR, 1.63; 95% CI, 1.32-2.02), weeks 5-12 (IR, 1.42; 95% CI, 1.21-1.68), and weeks 13-26 (IR, 1.23; 95% CI, 1.07-1.42), with no increase thereafter. A stronger effect was observed for individuals with zoster ophthalmicus, rising to a >3-fold rate 5-12 weeks after zoster. Oral antivirals were given to 55% of individuals: IRs for stroke were lower among those receiving antivirals compared with those not treated, suggesting a protective effect. Conclusions. We have established an increased stroke rate within 6 months following zoster. Findings have implications for zoster vaccination programs, which may reduce stroke risk following zoster. The low antiviral prescribing rate needs to be improved; our data suggest that antiviral therapy may lead to a reduced stroke risk following zoster.
    Clinical Infectious Diseases 04/2014; · 9.37 Impact Factor
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    ABSTRACT: A solid foundation of evidence of the effects of an intervention is a prerequisite of evidence-based medicine. The best source of such evidence is considered to be randomised trials, which are able to avoid confounding. However, they may not always estimate effectiveness in clinical practice. Databases that collate anonymised electronic health records (EHRs) from different clinical centres have been widely used for many years in observational studies. Randomised point-of-care trials have been initiated recently to recruit and follow patients using the data from EHR databases. In this review we describe how EHR databases can be used for conducting large-scale simple trials and discuss the advantages and disadvantages of their use. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 03/2014; · 6.46 Impact Factor
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    ABSTRACT: Objective To estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions. DesignPopulation-based cohort study. SettingLinked UK maternal–child primary care records. PopulationA total of 349 127 singletons liveborn between 1990 and 2009. Methods Odds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression. Main outcome measuresFourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups. ResultsAbsolute risks of MCA were 2.7% (95% confidence interval, 95% CI, 2.6–2.8%) in children of mothers without diagnosed depression, 2.8% (95% CI 2.5–3.2%) in children of mothers with unmedicated depression, and 2.7% (95% CI 2.2–3.2%) and 3.1% (95% CI 2.2–4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR 1.07, 95% CI 0.96–1.18), SSRIs (aOR 1.01, 95% CI 0.88–1.17), or TCAs (aOR 1.09, 95% CI 0.87–1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR 1.78, 95% CI 1.09–2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 95% CI 1.00–2.80). Conclusions Overall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.
    BJOG An International Journal of Obstetrics & Gynaecology 03/2014; · 3.76 Impact Factor
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    ABSTRACT: Obesity and type 2 diabetes (T2D) are highly prevalent among African migrants compared with European descent populations. The underlying reasons still remain a puzzle. Gene-environmental interaction is now seen as a potential plausible factor contributing to the high prevalence of obesity and T2D, but has not yet been investigated. The overall aim of the Research on Obesity and Diabetes among African Migrants (RODAM) project is to understand the reasons for the high prevalence of obesity and T2D among sub-Saharan Africans in diaspora by (1) studying the complex interplay between environment (eg, lifestyle), healthcare, biochemical and (epi)genetic factors, and their relative contributions to the high prevalence of obesity and T2D; (2) to identify specific risk factors within these broad categories to guide intervention programmes and (3) to provide a basic knowledge for improving diagnosis and treatment. RODAM is a multicentre cross-sectional study among homogenous sub-Saharan African participants (ie, Ghanaians) aged >25 years living in rural and urban Ghana, the Netherlands, Germany and the UK (http://rod-am.eu/). Standardised data on the main outcomes, genetic and non-genetic factors are collected in all locations. The aim is to recruit 6250 individuals comprising five subgroups of 1250 individuals from each site. In Ghana, Kumasi and Obuasi (urban stratum) and villages in the Ashanti region (rural stratum) are served as recruitment sites. In Europe, Ghanaian migrants are selected through the municipality or Ghanaian organisations registers. Ethical approval has been obtained in all sites. This paper gives an overview of the rationale, conceptual framework and methods of the study. The differences across locations will allow us to gain insight into genetic and non-genetic factors contributing to the occurrence of obesity and T2D and will inform targeted intervention and prevention programmes, and provide the basis for improving diagnosis and treatment in these populations and beyond.
    BMJ Open 01/2014; 4(3):e004877. · 1.58 Impact Factor
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    ABSTRACT: The population with stable coronary artery disease (SCAD) is growing but validated models to guide their clinical management are lacking. We developed and validated prognostic models for all-cause mortality and non-fatal myocardial infarction (MI) or coronary death in SCAD. Models were developed in a linked electronic health records cohort of 102 023 SCAD patients from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan-Meier 5-year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4, 9.9) for non-fatal MI or coronary death. The predictors in the models were age, sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety, heart rate, creatinine, white cell count, and haemoglobin. The models had good calibration and discrimination in internal (external) validation with C-index 0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or coronary death. Using these models to identify patients at high risk (defined by guidelines as 3% annual mortality) and support a management decision associated with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary event-free years per 1000 patients screened, compared with models with just age, sex, and deprivation. These validated prognostic models could be used in clinical practice to support risk stratification as recommended in clinical guidelines.
    European Heart Journal 12/2013; · 14.10 Impact Factor
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    ABSTRACT: Ethnicity recording across the National Health Service (NHS) has improved dramatically over the past decade. This study profiles the completeness, consistency and representativeness of routinely collected ethnicity data in both primary care and hospital settings. Completeness and consistency of ethnicity recording was examined in the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), and the ethnic breakdown of the CPRD was compared with that of the 2011 UK censuses. 27.1% of all patients in the CPRD (1990-2012) have ethnicity recorded. This proportion rises to 78.3% for patients registered since April 2006. The ethnic breakdown of the CPRD is comparable to the UK censuses. 79.4% of HES inpatients, 46.8% of outpatients and 26.8% of A&E patients had their ethnicity recorded. Amongst those with ethnicity recorded on >1 occasion, consistency was over 90% in all data sets except for HES inpatients. Combining CPRD and HES increased completeness to 97%, with 85% of patients having the same ethnicity recorded in both databases. Using CPRD ethnicity from 2006 onwards maximizes completeness and comparability with the UK population. High concordance within and across NHS sources suggests these data are of high value when examining the continuum of care. Poor completeness and consistency of A&E and outpatient data render these sources unreliable.
    Journal of Public Health 12/2013; · 2.06 Impact Factor
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    ABSTRACT: Serious adverse drug reactions are an important cause of hospitalisation and can result in the withdrawal of licensed drugs. Genetic variation has been shown to influence adverse drug reaction susceptibility, and predictive genetic tests have been developed for a limited number of adverse drug reactions. The identification of people with adverse drug reactions, obtaining samples for genetic analysis and rigorous evaluation of clinical test effectiveness represent significant challenges to predictive genetic test development. Using the example of serious drug-induced liver injury, we illustrate how a database of routinely collected electronic health records could be used to overcome these barriers by (1) facilitating rapid recruitment to genome-wide association studies and (2) supporting efficient randomized controlled trials of predictive genetic test effectiveness.
    Drug discovery today 11/2013; · 6.63 Impact Factor
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    ABSTRACT: Background. There is good evidence that respiratory and other infections that cause systemic inflammation can trigger strokes; however, the role of specific infections is unclear. Case-reports have highlighted chickenpox as a possible risk factor for arterial ischaemic stroke, particularly in children, but rigorous studies are needed to determine and quantify any increased risk. Methods. We used anonymised electronic health records totalling >100 million person-years of observation from four UK primary care databases to identify individuals who had documented clinical chickenpox and a stroke or transient ischaemic attack (TIA). Self-controlled case series methods were used to quantify any increased risk of first stroke or TIA in the 0-6 and 7-12 months following chickenpox compared to other observed time periods. We analysed data within each database, and performed meta-analyses to obtain summary age-adjusted incidence ratios (IR) separately for adults and children. Results. 560 eligible individuals (including 60 children) were identified who experienced chickenpox and a stroke or TIA during follow-up. Among children, there was a four-fold increased risk of stroke in the 0-6 months after chickenpox (summary IR=4.07; 95%CI=1.96-8.45, I(2)=0%). Among adults, there was a less marked increased risk with moderate between-database heterogeneity (random-effects summary IR=2.13, 95%CI=1.05-4.36; I(2)=51%). There was no significant increased risk of stroke in the 7-12 months after chickenpox in children or adults, nor was there evidence of increased risk of TIA in either time period. Conclusions. Our study provides new evidence that children who experience chickenpox are at increased risk of stroke in the subsequent 6 months.
    Clinical Infectious Diseases 10/2013; · 9.37 Impact Factor
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    ABSTRACT: It is widely thought that ST-elevation myocardial infarction (STEMI) is more likely to occur without warning (i.e. an unanticipated event in a previously healthy person) than non-ST-elevation myocardial infarction (NSTEMI), but no large study has evaluated this using prospectively collected data. The aim of this study was to compare the evolution of atherosclerotic disease and cardiovascular risk between people going on to experience STEMI and NSTEMI. We identified patients experiencing STEMI and NSTEMI in the national registry of myocardial infarction for England and Wales (Myocardial Ischaemia National Audit Project), for whom linked primary care records were available in the General Practice Research Database (as part of the CALIBER collaboration). We compared the prevalence and timing of atherosclerotic disease and major cardiovascular risk factors including smoking, hypertension, diabetes, and dyslipidaemia, between patients later experiencing STEMI to those experiencing NSTEMI. A total of 8174 myocardial infarction patients were included (3780 STEMI, 4394 NSTEMI). Myocardial infarction without heralding by previously diagnosed atherosclerotic disease occurred in 71% STEMI (95% CI 69-72%) and 50% NSTEMI patients (95% CI 48-51%). The proportions of myocardial infarctions with no prior atherosclerotic disease, major risk factors, or chest pain was 14% (95% CI 13-16%) in STEMI and 9% (95% CI 9-10%) in NSTEMI. The rate of heralding coronary diagnoses was particularly high in the 12 months before infarct; 4.1-times higher (95% CI 3.3-5.0) in STEMI and 3.6-times higher (95% CI 3.1-4.2) in NSTEMI compared to the rate in earlier years. Acute myocardial infarction occurring without prior diagnosed coronary, cerebrovascular, or peripheral arterial disease was common, especially for STEMI. However, there was a high prevalence of risk factors or symptoms in patients without previously diagnosed disease. Better understanding of the antecedents in the year before myocardial infarction is required.
    European heart journal. Acute cardiovascular care. 09/2013; 2(3):235-45.
  • European Urology 07/2013; · 10.48 Impact Factor
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    ABSTRACT: Time series regression studies have been widely used in environmental epidemiology, notably in investigating the short-term associations between exposures such as air pollution, weather variables or pollen, and health outcomes such as mortality, myocardial infarction or disease-specific hospital admissions. Typically, for both exposure and outcome, data are available at regular time intervals (e.g. daily pollution levels and daily mortality counts) and the aim is to explore short-term associations between them. In this article, we describe the general features of time series data, and we outline the analysis process, beginning with descriptive analysis, then focusing on issues in time series regression that differ from other regression methods: modelling short-term fluctuations in the presence of seasonal and long-term patterns, dealing with time varying confounding factors and modelling delayed ('lagged') associations between exposure and outcome. We finish with advice on model checking and sensitivity analysis, and some common extensions to the basic model.
    International Journal of Epidemiology 06/2013; · 6.98 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate targeting of statin prescribing for primary prevention to those with high cardiovascular disease (CVD) risk. DESIGN: Two cohort studies including the general population and initiators of statins aged 35-74 years. SETTING: UK primary care records in the Clinical Practice Research Datalink. PATIENTS: 3.8 million general population patients and 300 914 statin users. INTERVENTION: Statin prescribing. MAIN OUTCOME MEASURES: Statin prescribing by CVD risk; observed 5-year CVD risks; variability between practices. RESULTS: Statin prescribing increased substantially over time to patients with high 10-year CVD risk (≥20%): 7.0% of these received a statin prior to 2007, and 30.4% in 2007 onwards. Prescribing to patients with low risk (<15%) also increased (from 1.9% to 5.0%). Only about half the patients initiating statin treatment were high risk according to CVD risk score. The 5-year CVD risks, as observed during statin treatment, reduced over calendar time (from 17.0% to 7.1%). There was a large variation between general practices in the percentage of high-risk patients prescribed a statin in 2007 onwards, ranging from 8.2% to 61.5%. For low-risk patients, these varied from 2.1% to 29.1%. CONCLUSIONS: There appeared to be substantive overuse in low CVD risk and underuse in high CVD risk (600 000 and 850 000 patients, respectively, in the UK since 2007). There is wide variation between practices in statin prescribing to patients at high CVD risk. There is a clear need for randomised trials for the best strategy to target statin treatment and manage CVD risk for primary prevention.
    Heart (British Cardiac Society) 06/2013; · 5.01 Impact Factor
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    ABSTRACT: OBJECTIVE:: To determine the awareness, treatment, and control of hypertension and diabetes by migration status. DESIGN:: Cross-sectional study, secondary analyses of the PERU MIGRANT study. PATIENTS:: Rural, rural-to-urban migrants, and urban participants. MAIN OUTCOME MEASURES:: Awareness, treatment, and control of hypertension and diabetes mellitus were calculated using weights to account for participant's group size. RESULTS:: Of 205 of the 987 (weighted prevalence 24.1%, 95% confidence interval: 21.1%-27.1%) participants identified as hypertensive, 48.3% were aware of their diagnosis, 40% of them were receiving treatment, and 30.4% of those receiving treatment were controlled. Diabetes was present in 33 of the 987 (weighted prevalence 4.6%, 95% confidence interval: 3.1%-6%), and diabetes awareness, treatment, and control were 71.1%, 40.6%, and 7.7%, respectively. Suboptimal control rates, defined as those not meeting blood pressure or glycaemia targets among those with the condition, were 95.1% for hypertension and 97% for diabetes. Higher awareness, treatment, and control rates, for both hypertension and diabetes, were observed in rural-to-urban migrants and urban participants compared with rural participants. However, treatment rates were much lower among migrants compared with the urban group. CONCLUSIONS:: These results identify major unmet needs in awareness, treatment, and control of hypertension and diabetes. Particular challenges are lack of awareness of both hypertension and diabetes in rural areas, and poor levels of treatment and control among people who have migrated from rural into urban areas.
    Critical pathways in cardiology 06/2013; 12(2):53-58.
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    ABSTRACT: BACKGROUND: The role of antibiotics in treating mild or moderate exacerbations in patients with acute chronic obstructive pulmonary disease (COPD) is unclear. The aims were to: (i) describe patient characteristics associated with acute exacerbations amongst a representative COPD population, (ii) explore the relationship between COPD severity and outcomes amongst patients with exacerbations, and (iii) quantify variability by general practice in prescribing of antibiotics for COPD exacerbations. METHOD: A cohort of 62,747 patients with COPD was identified from primary care general practices (GP) in England, and linked to hospital admission and death certificate data. Exacerbation cases were matched to three controls and characteristics compared using conditional logistic regression. Outcomes were compared using incidence rates and Cox regression, stratified by disease severity. Variability of prescribing at the GP level was evaluated graphically and by using multilevel models. RESULTS: COPD severity was found to be associated with exacerbation and subsequent mortality (very severe vs. mild, odds ratio for exacerbation 2.12 [95%CI 19.5--2.32]), hazard ratio for mortality 2.14 [95%CI 1.59--2.88]). Whilst 61% of exacerbation cases were prescribed antibiotics, this proportion varied considerably between GP practices (interquartile range, 48--73%). This variation is greater than can be explained by patient characteristics alone. CONCLUSIONS: There is significant variability between GP practices in the prescribing of antibiotics to COPD patients experiencing exacerbations. Combined with a lack of evidence on the effects of treatment, this supports the need and opportunity for a large scale pragmatic randomised trial of the prescribing of antibiotics for COPD patients with exacerbations, in order to clarify their effectiveness and long term outcomes whilst ensuring the representativeness of subjects.
    BMC Pulmonary Medicine 05/2013; 13(1):32. · 2.76 Impact Factor
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    ABSTRACT: Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting. A cohort study of 766,330 fully eligible individuals aged ≥65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009. Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models. Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8-10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6-6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39-0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06-0.58). VE against PHN was 0.59 (95% CI 0.21-0.79). Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN. Please see later in the article for the Editors' Summary.
    PLoS Medicine 04/2013; 10(4):e1001420. · 15.25 Impact Factor
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    ABSTRACT: BACKGROUND: At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. METHODS: We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). RESULTS: The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. CONCLUSIONS: In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
    International Journal of Epidemiology 04/2013; 42(2):475-492. · 6.98 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: The prevalence of Huntington's disease (HD) in the UK is uncertain. Recently, it has been suggested that the prevalence may be substantially greater than previously reported. This study was undertaken to estimate the overall UK prevalence in adults diagnosed with HD, using data from primary care. METHODS: The electronic medical records of patients aged 21 years or more, with recorded diagnoses of HD, were retrieved from the UK's General Practice Research Database. Prevalence was estimated from the number of persons with recorded diagnoses of HD, on 1 July each year, between 1990 and 2010. This number was divided by the total number of persons registered with participating general practices on that same date. These data were also used to estimate both age specific prevalence and prevalence in various regions of the UK. RESULTS: A total of 1136 patients diagnosed with HD, aged 21 years or more, were identified from the database. The estimated prevalence (expressed per 100 000 population) rose from 5.4 (95% CI 3.8 to 7.5) in 1990 to 12.3 (95% CI 11.2 to 13.5) in 2010. Although an increased prevalence was observed within every age group, the most dramatic was in older patients. Age specific prevalence was highest in the 51-60 year age range (15.8 95% CI 9.0 to 22.3). The prevalence of adult HD was lowest in the London region (5.4 (95% CI 3.0 to 8.9)) and highest in the North East of England (18.3 (95% CI 8.6 to 34.6)) and Scotland (16.1 (95% CI 10.8 to 22.9)). CONCLUSIONS: The prevalence of diagnosed HD is clearly substantially higher in the UK than suggested from previous studies. By extrapolation to the UK as a whole, it is estimated that there are more than 5700 people, aged 21 years or more, with HD. There has also been a surprising doubling of the HD population between 1990 and 2010. Many factors may have caused this increase, including more accurate diagnoses, better and more available therapies and an improved life expectancy, even with HD. There also appears to be a greater willingness to register a diagnosis of HD in patients' electronic medical records. Such a high prevalence of HD requires more ingenuity and responsiveness in its care. How to appropriately care for, and respond to, so many individuals and families coping with the exigencies of HD demands our greatest resolve and imagination.
    Journal of neurology, neurosurgery, and psychiatry 03/2013; · 4.87 Impact Factor
  • Aine Skow, Ian Douglas, Liam Smeeth
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    ABSTRACT: AIM: To investigate whether the use of carbamazepine is associated with reduced risk of Parkinson's disease. METHODS: We conducted a population-based matched case-control study of patients randomly selected from the UK General Research Practice Database (GPRD). We identified 8,549 patients with Parkinson's disease using diagnosis criteria with a positive predictive value of 90%. These patients were compared with 42,160 controls matched for age, sex, and general practice. RESULTS: Overall, 3.0% of cases (257/8,549) had at least one recorded prescription for carbamazepine compared to 2.5% (1,050/42,160) of controls. The crude odds ratio (OR) for the association between Parkinson's disease and carbamazepine was 1.22 (95% confidence interval [CI]: 1.06-1.40), but this reduced to 0.93 (95%CI: 0.81-1.08, p=0.34) after adjusting for annual consultation rate. Further adjustment for body mass index, smoking status, alcohol consumption, or use of calcium channel blockers did not affect results. There was no evidence that risk decreased with higher doses or longer duration of carbamazepine use. CONCLUSIONS: There was little to no evidence that use of carbamazepine is associated with reduced risk of Parkinson's disease. Although the study was underpowered, it does indicate that any effect of carbamazepine is likely to be small.
    British Journal of Clinical Pharmacology 02/2013; · 3.58 Impact Factor
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    ABSTRACT: To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of antiepileptic drugs (AEDs) for refractory epilepsy. METHODS: We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialised register; MEDLINE (1950 to March 2009); EMBASE (1980 to March 2009); and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis. RESULTS: Forty-two eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only two direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio [OR] 3.78 [95% CI 3.14 to 4.55]) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritised oxcarbazepine, topiramate and pregabalin on the basis of short-term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritised on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognised as being associated with serious visual disturbance with chronic use. CONCLUSION: Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam, and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active-comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.
    British Journal of Clinical Pharmacology 01/2013; · 3.58 Impact Factor

Publication Stats

5k Citations
1,483.91 Total Impact Points

Institutions

  • 2000–2014
    • London School of Hygiene and Tropical Medicine
      • • Department of Non-communicable Disease Epidemiology
      • • Faculty of Epidemiology and Population Health
      Londinium, England, United Kingdom
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2013
    • Royal National Orthopaedic Hospital NHS Trust
      Londinium, England, United Kingdom
  • 2012
    • Aravind Eye Hospital
      Mathurai, Tamil Nādu, India
    • Medicines and Healthcare products Regulatory Agency (MHRA)
      Londinium, England, United Kingdom
  • 2010–2012
    • Universidad Peruana Cayetano Heredia
      • Centro de Excelencia en Enfermedades Crónicas
      Lima, LMA, Peru
    • Simon Fraser University
      Burnaby, British Columbia, Canada
  • 1998–2012
    • University College London
      • • Centre for Clinical Pharmacology and Theraputics
      • • Division of Medicine
      • • Department of Primary Care and Population Health (PCPH)
      London, ENG, United Kingdom
  • 2011
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2008–2011
    • University College London Hospitals NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2008–2010
    • Imperial College London
      Londinium, England, United Kingdom
  • 2009
    • University of Southampton
      Southampton, England, United Kingdom
    • Portsmouth Hospitals NHS Trust
      Portsmouth, England, United Kingdom
  • 2007–2009
    • University of Michigan
      • Division of Rheumatology
      Ann Arbor, MI, United States
    • Autonomous University of Bucaramanga
      Bucaramanga, Santander, Colombia
  • 1998–2008
    • University of Oxford
      • Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU)
      Oxford, ENG, United Kingdom
  • 2006
    • University of Wisconsin, Madison
      • Department of Medicine
      Madison, MS, United States
    • University of Nottingham
      • School of Clinical Sciences
      Nottingham, ENG, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2004
    • McGill University
      • Department of Psychiatry
      Montréal, Quebec, Canada