Liam Smeeth

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

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Publications (276)2067.57 Total impact

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    ABSTRACT: UK primary care databases are frequently used in observational studies with cancer outcomes. We aimed to systematically review methods used by such studies to identify and validate incident cancers of the breast, colorectum, and prostate. Medline and Embase (1980-2013) were searched for UK primary care database studies with incident breast, colorectal, or prostate cancer outcomes. Data on the methods used for case ascertainment were extracted and summarised. Questionnaires were sent to corresponding authors to obtain details about case ascertainment. Eighty-four studies of breast (n = 51), colorectal (n = 54), and prostate cancer (n = 31) were identified; 30 examined >1 cancer type. Among the 84 studies, 57 defined cancers using only diagnosis codes, while 27 required further evidence such as chemotherapy. Few studies described methods used to create cancer code lists (n = 5); or made lists available directly (n = 5). Twenty-eight code lists were received on request from study authors. All included malignant neoplasm diagnosis codes, but there was considerable variation in the specific codes included which was not explained by coding dictionary changes. Code lists also varied in terms of other types of codes included, such as in-situ, cancer morphology, history of cancer, and secondary/suspected/borderline cancer codes. In UK primary care database studies, methods for identifying breast, colorectal, and prostate cancers were often unclear. Code lists were often unavailable, and where provided, we observed variation in the individual codes and types of codes included. Clearer reporting of methods and publication of code lists would improve transparency and reproducibility of studies. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 11/2014; · 2.90 Impact Factor
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    ABSTRACT: It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation. Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997-2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme). During 11.6 million person-years of follow-up, 114 859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers' lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR) = 1.04, 95% confidence interval (CI) 0.91-1.19).The strength of association differed markedly according to disease type: stable angina (HR = 1.08, 95% CI 1.01-1.15),transient ischaemic attack (HR = 1.41, 95% CI 1.28-1.55), unstable angina (HR = 1.54, 95% CI 1.38-1.72), intracerebral haemorrhage (HR = 1.61, 95% CI 1.37-1.89), heart failure (HR = 1.62, 95% CI 1.47-1.79), ischaemic stroke (HR = 1.90, 95% CI 1.72-2.10), MI (HR = 2.32, 95% CI 2.20-2.45), SAH (HR = 2.70, 95% CI 2.27-3.21), PAD (HR = 5.16, 95% CI 4.80-5.54) and abdominal aortic aneurysm (AAA) (HR = 5.18, 95% CI 4.61-5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR = 1.36, 1.47 and 2.74, respectively). The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    International journal of epidemiology. 11/2014;
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    ABSTRACT: The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at (NCT01804439). Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]). Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. Wellcome Trust, National Institute for Health Research, and Medical Research Council. Copyright © 2014 Shah et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.
    The lancet. Diabetes & endocrinology. 11/2014;
  • Laurie Tomlinson, Liam Smeeth
    JAMA Internal Medicine 10/2014; 174(10):1706. · 13.25 Impact Factor
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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; · 3.69 Impact Factor
  • Ben Goldacre, Liam Smeeth
    BMJ Clinical Research 07/2014; 349:g4745. · 14.09 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: Our understanding of genome biology, genomics, and disease, and even hu-man history, has advanced tremen-dously with the completion of the Human Genome Project. Technologi-cal advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiol-ogy, diagnosis, and therapy for some of the world's most intractable and devastat-ing diseases—including ma-laria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, de-spite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only par-ticipated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on Afri-can participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants ( As discussed in 2011 (, if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent. The lack of large-scale genomics studies in Africa is the result of many deep-seated issues, including a shortage of African scien-tists with genomic research expertise, lack of biomedical research infrastructure, lim-ited computational expertise and resources, lack of adequate support for biomedical research by African governments, and the participation of many African scientists in collaborative research at no more than the level of sample collection. Overcoming these limitations will, in part, depend on African Enabling the genomic revolution in Africa By The H3Africa Consortium * H3Africa is developing capacity for health-related genomics research in Africa Yet, roughly a decade ago, newly pro-posed DNA-based taxonomy (11) promised to solve the species debate. A Barcode of Life Data Systems (BOLD) (12) quickly emerged, seeking to provide a reliable, cost-effective solution to the problem of species identification (12) and a standard screening threshold of sequence differ-ence (10× average intraspecific difference) to speed the discovery of new animal spe-cies (13). Sometimes considered a "carica-ture of real taxonomy" (14), this approach failed to identify, perhaps not surprisingly, two American crow species and a number of members of the herring gull Larus ar-gentatus species assemblage above the set threshold (13). Furthermore, despite past (3) and present (6) sequencing projects, carrion crows and hooded crows can also not be differentiated from one another by means of DNA-barcode approaches. By contrast, Poelstra et al. show that much more DNA sequencing data are needed, combined with RNA expression data, to reconstruct the evolution of a reproductive barrier that culminated in the speciation of these two crow taxa. Armed with this new very detailed genetic informa-tion, it is clear that none of the currently formulated species concepts fully apply to these two crow taxa (unless one is willing relax some stringency in the various definitions). In-deed, the genomes of German carrion crows are much more similar to those of hooded crows than to Spanish car-rion crows. Put simply, apart from the few carrion crow type "speciation islands," German carrion crows could be con-sidered to represent hooded crows with a black (carrion crow) phenotype. There is a clear need for ad-ditional population genomic studies using a more dense sampling, especially among the fully black carrion crows, before the complexity of repro-ductive isolation and speciation among these two taxa can be fully understood. The specia-tion genomics strategy already proved itself in unraveling the complexities of mimicry among many Heliconius butterfly taxa (7) and, as in the study of Poelstra et al., stresses the im-portance of using RNA-based information in addition to DNA. Only time will tell if, and when, German carrion crows will adopt the "hooded phenotype," a fate that seems un-avoidable. Until then, we can only applaud these crows for defeating Linnaeus's curse.
    Science 06/2014; 344(6190):1346-1348. · 31.03 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. · 39.21 Impact Factor
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    ABSTRACT: To quantify the effects of possible risk factors for herpes zoster at different ages.
    BMJ Clinical Research 05/2014; 348:g2911. · 14.09 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.
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    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.

Publication Stats

6k Citations
2,067.57 Total Impact Points


  • 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
    • 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
    • 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