Liam Smeeth

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

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Publications (267)1998.18 Total impact

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    ABSTRACT: AimsThis was a cohort study to evaluate if individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors.Methods The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year.ResultsA total of 426,089 persons were included in the primary analysis, with 45,541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6,517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after start of treatment (adjusted hazard ratio 0.92, 95% CI 0.85-1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% CI 0.50-0.72).ConclusionsA small reduction in dementia risk was seen with angiotensin receptor blockers compared with angiotensin-converting enzyme inhibitors. However the strongest association was seen in early follow-up suggesting the inverse association is unlikely to be causal, but reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.
    British Journal of Clinical Pharmacology 09/2014; · 3.58 Impact Factor
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    ABSTRACT: Ischaemia in different arterial territories before acute myocardial infarction (AMI) may influence post-AMI outcomes. No studies have evaluated prospectively collected information on ischaemia and its effect on short- and long-term coronary mortality. The objective of this study was to compare patients with and without prospectively measured ischaemic presentations before AMI in terms of infarct characteristics and coronary mortality.
    European heart journal. 07/2014;
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    ABSTRACT: To inform potential pathophysiological mechanisms of air pollution effects on cardiovascular disease (CVD), we investigated short-term associations between ambient air pollution and a range of cardiovascular events from three national databases in England and Wales.
    Heart (British Cardiac Society) 07/2014; 100(14):1093-1098. · 5.01 Impact Factor
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    ABSTRACT: There is strong evidence of reductions in major vascular events from statins across all cardiovascular risk categories. However, trials of statin therapy have provided conflicting results regarding statin use and type 2 diabetes (T2DM). We aimed to assess the effect of statins on T2DM development.
    BMC Cardiovascular Disorders 07/2014; 14(1):85. · 1.46 Impact Factor
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    ABSTRACT: Antipsychotics increase the risk of stroke. Their effect on myocardial infarction remains uncertain because people prescribed and not prescribed antipsychotic drugs differ in their underlying vascular risk making between-person comparisons difficult to interpret. The aim of our study was to investigate this association using the self-controlled case series design that eliminates between-person confounding effects.
    European heart journal. 07/2014;
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    ABSTRACT: Pragmatic trials compare the effects of different decisions in usual clinical practice.
    Health technology assessment (Winchester, England) 07/2014; 18(43):1-146. · 4.03 Impact Factor
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    ABSTRACT: The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.
    The Lancet 05/2014; 383(9932):1899-911. · 39.06 Impact Factor
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    ABSTRACT: Historically, health facilities in sub-Saharan Africa have mainly managed acute, infectious diseases. Few data exist for the preparedness of African health facilities to handle the growing epidemic of chronic, non-communicable diseases (NCDs). We assessed the burden of NCDs in health facilities in northwestern Tanzania and investigated the strengths of the health system and areas for improvement with regard to primary care management of selected NCDs. Between November, 2012, and May, 2013, we undertook a cross-sectional survey of a representative sample of 24 public and not-for-profit health facilities in urban and rural Tanzania (four hospitals, eight health centres, and 12 dispensaries). We did structured interviews of facility managers, inspected resources, and administered self-completed questionnaires to 335 health-care workers. We focused on hypertension, diabetes, and HIV (for comparison). Our key study outcomes related to service provision, availability of guidelines and supplies, management and training systems, and preparedness of human resources. Of adult outpatient visits to hospitals, 58% were for chronic diseases compared with 20% at health centres, and 13% at dispensaries. In many facilities, guidelines, diagnostic equipment, and first-line drug therapy for the primary care of NCDs were inadequate, and management, training, and reporting systems were weak. Services for HIV accounted for most chronic disease visits and seemed stronger than did services for NCDs. Ten (42%) facilities had guidelines for HIV whereas three (13%) facilities did for NCDs. 261 (78%) health workers showed fair knowledge of HIV, whereas 198 (59%) did for hypertension and 187 (56%) did for diabetes. Generally, health systems were weaker in lower-level facilities. Front-line health-care workers (such as non-medical-doctor clinicians and nurses) did not have knowledge and experience of NCDs. For example, only 74 (49%) of 150 nurses had at least fair knowledge of diabetes care compared with 85 (57%) of 150 for hyptertension and 119 (79%) of 150 for HIV, and only 31 (21%) of 150 had seen more than five patients with diabetes in the past 3 months compared with 50 (33%) of 150 for hypertension and 111 (74%) of 150 for HIV. Most outpatient services for NCDs in Tanzania are provided at hospitals, despite present policies stating that health centres and dispensaries should provide such services. We identified crucial weaknesses (and strengths) in health systems that should be considered to improve primary care for NCDs in Africa and identified ways that HIV programmes could serve as a model and structural platform for these improvements. UK Medical Research Council.
    The lancet global health. 05/2014; 2(5):e285-e292.
  • 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: Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data. We used data from 18 712 adults admitted to Kilifi District Hospital (Kilifi, Kenya) between Jan 1, 2007, and Dec 31, 2012, linked to 790 635 person-years of observation within the Kilifi Health and Demographic Surveillance System, to establish the rates and major causes of admission to hospital. These data were also used to model disease-specific disability-adjusted life-years lost in the population. We used geographical mapping software to calculate admission rates stratified by distance from the hospital. The main causes of admission to hospital in women living within 5 km of the hospital were infectious and parasitic diseases (303 per 100 000 person-years of observation), pregnancy-related disorders (239 per 100 000 person-years of observation), and circulatory illnesses (105 per 100 000 person-years of observation). Leading causes of hospital admission in men living within 5 km of the hospital were infectious and parasitic diseases (169 per 100 000 person-years of observation), injuries (135 per 100 000 person-years of observation), and digestive system disorders (112 per 100 000 person-years of observation). HIV-related diseases were the leading cause of disability-adjusted life-years lost (2050 per 100 000 person-years of observation), followed by non-communicable diseases (741 per 100 000 person-years of observation). For every 5 km increase in distance from the hospital, all-cause admission rates decreased by 11% (95% CI 7-14) in men and 20% (17-23) in women. The magnitude of this decline was highest for endocrine disorders in women (35%; 95% CI 22-46) and neoplasms in men (30%; 9-45). Adults in rural Kenya face a combined burden of infectious diseases, pregnancy-related disorders, cardiovascular illnesses, and injuries. Disease burden estimates based on hospital data are affected by distance from the hospital, and the amount of underestimation of disease burden differs by both disease and sex. The Wellcome Trust, GAVI Alliance.
    The lancet global health. 01/2014; 2(4):e216-e224.
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    ABSTRACT: Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy.
    PLoS ONE 01/2014; 9(6):e100996. · 3.53 Impact Factor
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    ABSTRACT: The UK government recommends that at least 75% of people aged under 64 with certain conditions receive an annual influenza vaccination. Primary care practices often fall short of this target and strategies to increase vaccine uptake are required. Text messaging reminders are already used in 30% of practices to remind patients about vaccination, but there has been no trial addressing their effectiveness in increasing influenza vaccine uptake in the UK. The aims of the study are (1) to develop the methodology for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records and (2) to assess the effectiveness of using a text messaging influenza vaccine reminder in achieving an increase in influenza vaccine uptake in patients aged 18-64 with chronic conditions, compared with standard care. This cluster randomised trial will recruit general practices across three settings in English primary care (Clinical Practice Research Datalink, ResearchOne and London iPLATO text messaging software users) and randomise them to either standard care or a text messaging campaign to eligible patients. Flu vaccine uptake will be ascertained using routinely collected, anonymised electronic patient records. This protocol outlines the proposed study design and analysis methods. This study will determine the effectiveness of text messaging vaccine reminders in primary care in increasing influenza vaccine uptake, and will strengthen the methodology for using electronic health records in cluster randomised trials of text messaging interventions. This trial was approved by the Surrey Borders Ethics Committee (13/LO/0872). The trial results will be disseminated at national conferences and published in a peer-reviewed medical journal. The results will also be distributed to the Primary Care Research Network and to all participating general practices. This study is registered at controlled-trials.com ISRCTN48840025, July 2013.
    BMJ Open 01/2014; 4(5):e004633. · 1.58 Impact Factor
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    ABSTRACT: Background High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. Methods With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. Findings 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. Interpretation BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. Funding National Institute for Health Research, Wellcome Trust, and Medical Research Council.
    Lancet. 01/2014;
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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 optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.
    BMJ Open 01/2014; 4(7):e005540. · 1.58 Impact Factor
  • Ben Goldacre, Liam Smeeth
    BMJ Clinical Research 01/2014; 349:g4745. · 14.09 Impact Factor
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    ABSTRACT: To quantify the effects of possible risk factors for herpes zoster at different ages.
    BMJ Clinical Research 01/2014; 348:g2911. · 14.09 Impact Factor

Publication Stats

6k Citations
1,998.18 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
  • 2013
    • Royal National Orthopaedic Hospital NHS Trust
      Londinium, England, United Kingdom
  • 2012
    • Medicines and Healthcare products Regulatory Agency (MHRA)
      Londinium, England, United Kingdom
    • Aravind Eye Hospital
      Mathurai, Tamil Nādu, India
  • 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
  • 2010–2011
    • Universidad Peruana Cayetano Heredia
      • Centro de Excelencia en Enfermedades Crónicas
      Lima, LMA, Peru
    • Simon Fraser University
      Burnaby, British Columbia, Canada
  • 2008–2011
    • University College London Hospitals NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2008–2010
    • Imperial College London
      Londinium, England, United Kingdom
  • 2009
    • Portsmouth Hospitals NHS Trust
      Portsmouth, England, United Kingdom
    • University of Southampton
      Southampton, 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 Nottingham
      • School of Clinical Sciences
      Nottingham, ENG, United Kingdom
    • University of London
      Londinium, England, United Kingdom
    • University of Wisconsin, Madison
      • Department of Medicine
      Madison, MS, United States
  • 2004
    • McGill University
      • Department of Psychiatry
      Montréal, Quebec, Canada