Population Health
UCL School of Life and Medical Sciences
Creating knowledge, achieving impact
4
PREFACE
UCL’s School of Life and Medical
Sciences encompasses arguably the
greatest concentration of biomedical
science and population health
expertise in Europe. Our performance
in the UK’s last Research Assessment
Exercise was outstanding, and for most
key measures the School comfortably
tops UK league tables.
In part because of UCL’s size and
organisational complexity, the scale
of its achievements is not always
apparent. This publication, one of
four, seeks to address this. Our recent
reorganisation, with the creation of
four new Faculties, has been designed
to create a more coherent structure,
of which the Faculty of Population
Health Sciences headed by the Dean,
Professor Graham Hart, is a clear
example. But the School’s restructuring
has also placed great emphasis
on cross-Faculty interactions and
interdisciplinary research – and indeed
on interactions with departments
outside the School across UCL.
Such interdisciplinary endeavour is
promoted through the establishment
of ‘Domains’, inclusive strategically led
fluid networks. Nowhere is this more
important than in the field of population
health given its myriad determinants
– including, for example, economic
status, the built environment and
cultural differences in health beliefs,
as well as more obvious genetic and
environmental factors. Professor Anne
Johnson chairs UCL’s Population
Health Domain, working closely with
the Faculty as well as colleagues in
other disciplines.
UCL is acutely aware that scientific
advance of real relevance to society
is not only aided by an interdisciplinary
approach but also through
collaborative strategic alliances with
other research-intensive institutions
with complementary strengths.
Our founding partner status in the
new Francis Crick Institute engages
us in what will be the European
powerhouse of biomedical research
expertise. In the population health
field our growing collaboration with
our Bloomsbury neighbours, the
London School of Hygiene and
Tropical Medicine, is fuelling exciting
developments in the fields of genetic
epidemiology and pathogen research
and we are both proud to be members
of the new NIHR School for Public
Health Research.
The breadth and quality of our
research creates almost unique
opportunities. Whatever an individual’s
interests, there is likely to be a worldleading expert with complementary
interests nearby. Thanks to our size,
we have been able to establish support
services and platform technologies
to accelerate research. Our highly
productive links to the health service,
through UCL Partners, provides
access to unmatched clinical expertise
and large patient groups.
The School’s academic environment
is one in which intellectual curiosity
can prosper, while a high priority is
also given to the practical application
of knowledge to improve health and
quality of life. This can take many
forms, including commercialisation of
new products as well as developing
and informing health and social
policy, and engaging with important
stakeholders, including the public.
In keeping with UCL’s traditions,
there is a radical element to our work,
with national and global inequalities
a key concern.
This publication, one of four (see right),
showcases some of the outstanding
research in population health being
carried out within the School and with
collaborators across UCL, in London,
nationally and internationally. It is
impossible to be comprehensive, but
the stories give a flavour of the breadth,
quality and impact of the School’s
research. Looking forward, our aims
are to enhance and expand our
research to ensure we remain a global
leader, and to see more people benefit
from the groundbreaking research
being carried out across the School.
Sir John Tooke
Vice-Provost (Health) and
Head of the UCL School of Life
and Medical Sciences.
1
Basic Life Sciences:
‘Discovery’ research, from
molecules to ecosystems.
2
Translation and
Experimental Medicine:
Driving translation to
benefit patients’ health
and well-being.
3
Neuroscience and
Mental Health:
The science of the brain
and nervous system,
from synapse to social
interactions.
4
Population Health:
Protecting and improving
the health of populations,
UK and globally.
CONTENTS
Overview: The health of the people
2
The aim of UCL’s Population Health research is to keep people
healthier for longer and to reduce health inequalities.
Section 1: Women and children first
4
How cohort- and community-based studies help to safeguard
the health of women and infants.
Feature: Let’s talk about sex: The National Survey of Sexual
Attitudes and Lifestyles
12
Section 2: Young people and transition to adulthood
14
A succession of birth cohorts has shed light on the health,
development and welfare of generations of UK children.
20
Section 3: The middle years
How adult life is shaped by past experience, and influences
our ‘third age’.
Feature: The heart of the civil service: The Whitehall studies
30
Section 4: How to age successfully
32
Population studies have highlighted key factors contributing to
a healthy old age.
Feature: Sixty-five years young: The 1946 Birth Cohort
38
Section 5: Global health research
40
Tackling public health threats outside the UK, from maternal health
to climate change.
UCL institutes, support services, partners, funding and sponsors.
46
POPULATION HEALTH UCL School of Life and Medical Sciences
1
The health of
the people
The aim of UCL’s Population Health
research is to keep people healthier
for longer and to reduce health
inequalities.
Jeremy Bentham, an
influential figure in UCL’s
history, is perhaps best
known for his utilitarian ethics
– promoting “the greatest
good for the greatest number
of people”. While that may
not exactly translate to UCL’s
current Population Health
research, it does capture a
flavour of the domain’s aims.
Modern science has proven
remarkably successful at
developing interventions
that, unlike most remedies
from previous eras, actually
work. More are needed, of
course, but their success
has transformed the health
landscape of the UK,
generating new priorities:
how do we prevent people
becoming ill? How do we
deal with chronic conditions?
How can we deliver
healthcare most effectively?
Moreover, health is not
simply ‘absence of disease’
but encompasses quality of
life and mental well-being,
not just for their own sake
but also because they can
protect from physical and
mental ill-health.
2
If a goal is a Bentham-esque
“the greatest health for the
greatest number of people”,
where should attention be
focused? On the one hand,
almost every aspect of
modern life has some impact
on our health – what we
eat, what exercise we take,
what germs we encounter,
how we are treated by
others, whether we smoke,
what happens at work (if
we have a job). How these
factors affect our health is
complex, subtle and difficult
to disentangle. Exposure to
a virus might render us sick
within a few days; an extra
burger every week might
take decades to have an
effect. Moreover, influences
accumulate over a lifetime.
Our education, how we
were parented, even our
birthweight can influence
how healthy we are years
and decades later.
On the other hand, when our
health does fail, we rely on
the NHS to put it right. Our
first port of call is usually our
GP and primary care; we
may then be referred on to
...birth cohorts have focused attention on
the long-lasting effects of early-life events,
highlighting childhood as a crucial phase to
intervene not just for the immediate benefit of
children but to alter the trajectory of entire lives.
specialist secondary care.
Collectively, these systems
account for a substantial
proportion of national
expenditure, and play a
big part in maintaining the
nation’s health.
A research agenda
The Population Health
research agenda therefore
spans work within healthcare
systems (principally primary
care) and within society.
The common questions are:
how do we keep people
healthier for longer? And
how do we ensure that health
gains are shared equitably?
Large cohorts (healthy
populations as well as
patients) are a major focus:
UCL researchers lead healthrelated studies on several
major cohorts, including
the UK’s national birth
POPULATION HEALTH UCL School of Life and Medical Sciences
cohorts (1946, 1958 and
2000). Some £28 million has
recently been announced for
a major new birth cohort, led
by Professor Carol Dezateux.
UCL has also played a major
role in the groundbreaking
‘Whitehall’ cohorts. In
Whitehall I, Professor Sir
Michael Marmot identified
a strong ‘socioeconomic
gradient’ – people’s health
was dependent on their
position within a social
hierarchy. These findings
helped to establish the field
of healthcare inequalities,
in which Professor Marmot
remains a world-recognised
authority.
Birth cohorts – and
comparisons between them
– have also emphasised the
‘life course’ perspective on
disease. Health is dependent
on past experience as well
as current circumstances.
In particular, birth cohorts
have focused attention on
the long-lasting effects of
early-life events, highlighting
childhood as a crucial phase
to intervene not just for the
immediate benefit of children
but to alter the trajectory of
entire lives.
Cohorts have traditionally
focused on environmental
influences, but are
increasingly integrating
genetic approaches.
Genes influence biology
and health throughout life.
Moreover, there is extensive
crosstalk between genes
and environment – it is
increasingly meaningless
to talk about the effects
of nature and nurture as
the two are so intertwined.
Technological advances
have paved the way for
large-scale genetic studies,
ushering in a new era of
‘genomic epidemiology’.
Disease-specific cohorts are
also important, particularly
in HIV research. UCL
researchers have been
involved in some of the
world’s largest and longestrunning HIV patient cohorts,
providing key information
on treatment and drug
resistance.
Study of health behaviours
is becoming an increasingly
important area. Considerable
work is undertaken to
document behaviours
relevant to health, for
example Health Surveys
for England and the
National Survey of Sexual
Attitudes and Lifestyles
(Natsal). Other projects
have attempted to modify
behaviours – not always, it
has to be said, with a great
deal of success. There is
thus a need to gain a better
understanding of why people
behave as they do and
what kinds of interventions
lead to behaviour change
at individual and population
levels.
Primary care
UCL has major programmes
of research in primary care,
particularly around mental
health and ageing, with
several nationally important
trials being coordinated in
the ‘Priment’ Clinical Trials
Unit. A large programme of
applied health research is
examining issues around
healthcare organisation
and delivery. UCL
researchers also contribute
to the development of
health policy, as advisers to
the Department of Health,
through work on advisory
committees and drafting
guidelines for bodies such
as the National Institute
for Health and Clinical
Excellence (NICE).
‘Data mining’ of electronic
patient records is a further
important focus. With
the NHS, the UK is in the
enviable position of having
centrally coordinated data
collection, offering enormous
opportunities for analysis
of routinely captured data
to guide practice. UCL
researchers have helped
to develop data standards
to facilitate effective use of
health records, and many
studies have analysed health
record data in centralised
repositories. An ‘e-health’
initiative aims to harness the
enormous potential of the
web and new technologies to
deliver interventions to large
numbers of people.
PARTNERS FOR HEALTH
By working closely with institutions delivering
healthcare, UCL aims to ensure that its research
benefits local populations.
UCL has forged close links
with some of London’s
leading clinical centres. It has
established UCL Partners
with UCL Hospitals NHS
Foundation Trust, the Royal
Free Hampstead NHS Trust,
Moorfield’s Eye Hospital NHS
Foundation Trust and Great
Ormond Street Hospital for
Children NHS Trust. In 2009,
UCL Partners was designated
one of the UK’s first five
Academic Health Science Centres. Its 11 priority areas reflect both
UCL research strengths and local health priorities.
UCL Partners aims to improve the health of communities in
London and beyond served by its NHS members. Translation
is further supported by the presence of three NIHR Biomedical
Research Centres within UCL Partners – at UCLH, Moorfields and
Great Ormond Street. New £165m five-year funding was awarded
in 2011 by the NIHR, including support for a new Biomedical
Research Unit specialising in dementia.
UCL Partners is also a member of the North East London,
North Central London and Essex (NECLES) Health Innovation
and Education Cluster, with North-East London Health and Anglia
Ruskin University and its health-service partners. Collectively,
NECLES covers 5.8 million people (10 per cent of the UK
population) and accounts for 10 per cent of NHS expenditure.
A key aim of NECLES, and of a cross-cutting public health
programme at UCL Partners, is to identify ways in which healthcare
inequalities can be tackled.
Ultimately, impact on people is likely to come through translation
of promising laboratory science, improved delivery of healthcare,
and initiatives in public health – all validated by rigorous research.
Indeed, a major challenge is to integrate public services that protect
and improve health, whether they fall within public health, primary
care, secondary care or even social care – creating a ‘national
health system’ that takes a citizen’s-eye view of health and wellbeing from cradle to grave.
The wider context
and globalisation, all with
enormous potential to
impact on health, have led to
productive partnerships with
a wide range of disciplines,
from philosophy to urban
planning.
The scope of population
health studies is broad.
With an increasing
appreciation of the wide
range of factors affecting
health – and their economic
and sociopolitical context
– research increasingly
draws upon expertise in
other areas of UCL. The
momentous changes in
the ‘anthropocene’ era –
climate change, ecosystem
destruction, urbanisation
This naturally promotes
a focus on global health
issues. UCL has established
an Institute for Global Health
with its Grand Challenge
Programme and helped to
raise awareness of the health
effects of climate change,
particularly through the
UCL–Lancet Commission,
set up to focus attention on
the potentially catastrophic
impact of global climate
change on health.
UCL researchers also carry
out important research
overseas, particularly in Asia
and Africa, where Professor
Anthony Costello and
colleagues have pioneered a
participatory approach to the
development of community
interventions to improve
neonatal health.
UCL therefore aims to have
an impact at local, national
and international levels.
A common theme is the
insidious impact of social
inequalities. Identifying these
inequalities and how they
come about – and trying to
do something about them –
is a core principle. Jeremy
Bentham would surely have
approved.
POPULATION HEALTH UCL School of Life and Medical Sciences
3
SECTION 1
Women and
children first
The health of women and infants is rightly a high
priority. Cohort- and community-based studies
have done much to safeguard the health of both
mothers and their babies. A major challenge now
is to develop services that are organised around
women’s needs and recognise the importance
of life-course influences.
4
POPULATION HEALTH School of Life and Medical Sciences
Childbirth was once the
leading cause of death for
women. Thanks to better
healthcare and important
social changes, death in
childbirth is now extremely
rare and neonatal mortality
also greatly reduced (at least
in developed countries).
Recent years have seen
greater survival of premature
babies. The gestational
age at which premature
babies can survive has been
progressively pushed back,
through the use of steroids to
promote lung development
and surfactants to improve
breathing after birth, as well
as advances in paediatric
intensive care.
This might seem like an
unqualified success, but
saving the lives of extremely
pre-term infants does have
consequences. These
have been documented in
a unique long-term study,
EPICure, which since 1995
has followed the progress
of a cohort of babies born
before 25 weeks (see page
7). Many of these infants had
disabilities, and others have
gone on to suffer problems
with physical health (such
as respiratory conditions)
and mental development
during childhood. Run in
A lack of oxygen at birth – birth asphyxia – is one
of the most common problems at birth, potentially
leading to oxygen starvation and damage to the
brain and, in the most severe cases, death.
partnership with Nottingham
and Warwick, EPICure
is continuing to follow its
cohort as they approach
adolescence and adulthood.
Its findings have been highly
influential in policy debates
about extreme prematurity.
mild cooling – now the
recommended treatment
in the UK (see page 8 ).
Interestingly, the noble gas
xenon – coincidentally,
discovered at UCL in the
19th century – may offer
additional protection.
Lung function is one of the
most critical aspects of birth,
as a newborn begins to
acquire oxygen from the air
around it. A lack of oxygen
at birth – birth asphyxia –
is one of the most common
problems at birth, potentially
leading to oxygen starvation
and damage to the brain
and, in the most severe
cases, death.
Cooling could have even
more impact in developing
countries, where birth
asphyxia is very common.
Dr Nikki Robertson and
colleagues have explored
the potential application of
the procedure in resourcepoor settings, using locally
available materials (such as
widely used water bottles to
hold cooled water). However,
considerable thought needs
to be given to implementation
in countries with less welldeveloped healthcare
infrastructures, especially
when the potential for harm
is great if techniques are
misapplied. Currently work
is underway to assess the
feasibility of undertaking
a trial.
Research at UCL has had
significant impact in this
area. Advances in infant
brain imaging, used to
monitor energy expenditure,
revealed a gap between
oxygen starvation and
subsequent death of nerve
cells. Researchers have
sought ways to intervene
in this window to prevent
damage, one of the
most successful being
POPULATION HEALTH UCL School of Life and Medical Sciences
5
The UCL Centre for Prenatal Genetic Diagnosis
(PGD) was one of the first centres in the world
to offer PGD, and continues to combine research
with clinical service, advancing understanding of
early human development as well as improving
clinical practice.
Much research in this area is
undertaken at UCL Elizabeth
Garrett Anderson Institute
for Women’s Health, which
enjoys a close relationship
with University College
London Hospital. In spring
2011 Professor Peter
Brocklehurst moved from
the University of Oxford to
take over as Director, having
previously collaborated
extensively with researchers
at the Institute. Professor
Brocklehurst is one of the
UK’s leading figures in
perinatal research and is
leading a number of trials of
perinatal care.
The Institute’s research
covers four main themes:
gynaecological cancer,
maternal and fetal
medicine, neonatology
and reproductive health.
Research on gynaecological
6
cancers, led by former
Institute Director Professor
Ian Jacobs and Professor
Usha Menon, has been
particularly notable. An
important focus has been
early detection of ovarian
cancer, including large
clinical trials assessing the
value of different screening
approaches (the UKCTOCS
and FOCSS trials; see
page 7).
A key theme in maternal and
fetal medicine is prenatal
screening and prenatal
genetic diagnosis (PGD).
Professor Lyn Chitty,
for example, is leading a
five-year multicentre study
exploring the potential of
analysing fetal DNA in the
maternal bloodstream to
diagnose Down syndrome.
The UCL Centre for PGD
was one of the first centres
in the world to offer PGD,
and continues to combine
research with clinical service,
advancing understanding of
early human development
as well as improving clinical
practice.
An important recent move
has been the appointment
of Professor Kypros
Nicolaides, who now holds
a joint appointment at UCL
and King’s College London.
A world-leading figure in
fetal medicine, Professor
Nicolaides’ research interests
include early screening
for fetal abnormalities and
pregnancy complications.
In collaboration with medical
staff at Great Ormond Street
Hospital, UCL researchers
have also carried out
innovative studies on postmortem magnetic resonance
imaging of fetuses. There
are understandable
sensitivities about fetal
post-mortems, particularly
among some ethnic minority
communities. Clinical trials
comparing conventional and
non-invasive approaches
POPULATION HEALTH UCL School of Life and Medical Sciences
suggest that high-resolution
MRI could offer a noninvasive alternative way
of characterising tissue
damage.
Population-based
reproductive health research
covers a range of areas,
including an evaluation
by Professor Judith
Stephenson and colleagues
of England’s National
Teenage Pregnancy Strategy
(see page 11). In terms
of interventions, a large
randomised controlled trial
of peer-led sex education,
RIPPLE, involved long-term
(seven-year) follow up in
27 schools in England. The
peer-led approach was
popular with school students,
and may have reduced
the number of live births,
but abortion rates were the
same as in groups receiving
teacher-led sex education1.
1 Stephenson J et al. The long-term
effects of a peer-led sex education
programme (RIPPLE): a cluster
randomised trial in schools in England.
PLoS Med. 2008;5(11):e224.
Screening under the microscope
Too much too young?
The EPICure study has identified a host of long-term issues
associated with extreme pre-term birth.
Over the past decades great strides have been made in the survival
of extremely pre-term infants. While a young life saved might seem an
incontrovertible good thing, it soon became apparent that prematurity
had significant consequences. The EPICure study was set up to
assess this impact systematically, and has documented a wide-range
of issues associated with extreme prematurity as children develop.
Begun in 1995, the EPICure study, led by Professor Neil Marlow
with colleagues in Nottingham, Queen Mary College, Sheffield and
Warwick, is an ambitious and influential study of all births before 25
weeks and 6 days gestation. The 314 survivors have been followed
ever since, with major assessments at age six and age 11. The study’s
findings have shed important light on the challenges faced by these
children and their families, and done much to shape policy in the
difficult area of extremely pre-term birth.
At 30 months, 24 per cent of survivors were categorised as having
severe difficulties. By age six, a comparison with peers revealed
significant deficits, particularly in cognitive performance – almost
twice as many, 41 per cent, showed general cognitive deficits.
Assessments at 11 years of age have shown increased risk for
behavioural and emotional disorders, with extremely preterm children
being more than three times more likely to have a psychiatric disorder
than classmates (23 per cent). Around one in eight attended special
schools and more than half of those in mainstream education had
special educational needs. The children also showed physical
problems, with 78 per cent showing abnormalities in lung function.
The EPICure study has also begun to assess both the economic
and personal impact of extreme prematurity, using quality of life
questionnaires. Planning is underway to survey the participants again
at age 19. In 2006, a follow-up study, EPICure2, was launched. This
has documented a significant increase in the number of babies born
extremely pre-term, but survival is improving and infants are now less
likely to be seriously affected. This unique study is thus continuing to
provide objective data on a particularly difficult area of health policy.
Marlow N et al. Neurologic and developmental disability at six years of age
after extremely preterm birth. N Engl J Med. 2005;352(1):9–19.
Lum S et al. Nature and severity of lung function abnormalities in extremely
pre-term children at 11 years of age. Eur Respir J. 2011;37(5):1199–207.
Johnson S et al. Psychiatric disorders in extremely preterm children:
longitudinal finding at age 11 years in the EPICure study. J Am Acad Child
Adolesc Psychiatry. 2010;49(5):453–63.e1.
Johnson S et al. Academic attainment and special educational needs in
extremely preterm children at 11 years of age: the EPICure study. Arch Dis
Child Fetal Neonatal Ed. 2009;94(4):F283–9.
Petrou S et al. Economic costs and preference-based health-related quality of
life outcomes associated with childhood psychiatric disorders. Br J Psychiatry.
2010;197:395–404.
Large trials will reveal whether screening for ovarian
cancer can save lives?
Ovarian cancer is the most common gynaecological cancer and
the fifth leading cause of death from cancer in women. As it is
often detected late, survival rates are poor. There is therefore
great interest in screening to detect cancer at earlier stages,
when survival rates are much higher. Professor Usha Menon,
Professor Ian Jacobs and colleagues are running large-scale
trials to assess whether two screening techniques – a blood test
and ultrasound – are suitable for widespread implementation.
The first trial, UKCTOCS, is a randomised controlled trial
comparing a blood test for CA-125 (a well-known marker for
ovarian cancer) interpreted using a novel algorithm, transvaginal
ultrasound and a control arm where screening is not used. The
primary aim is to see whether screening will prevent deaths
from ovarian cancer. The trial is also addressing psychological
impacts, possible drawbacks (complications in women
undergoing surgery after false positive results) and the financial
cost of screening, and whether strategies based on a blood test
or ultrasound would be more feasible for population screening.
Involving some 202,000 women, the trial is the largest of its
kind in the world. In the preliminary results from 100,000 women
in the screen arms of the trial, ovarian cancer was identified in
87 women and missed by screening in 13 women. These results
are encouraging and suggest that either of the two approaches
could potentially be used in population screening programmes.
However, a definitive answer will depend on the results of
continued annual screening and long-term follow-up. This is due
to be completed in 2014, when it will be clear whether screening
has sufficient benefits on mortality to be worth implementing.
A second trial, UKFOCCS, is targeting a specific population,
those with either a family history of ovarian cancer or mutations in
the breast cancer genes BRCA1 or BRCA2, which also increase
the risk of ovarian cancer. The trial is assessing the value of fourmonthly blood tests and an annual ultrasound for this high-risk
group. Around 5000 women are participating, and the study is
due to complete by 2013.
Professor Menon and colleagues are also leading the UK’s
contribution to an international collaboration, the Ovarian Cancer
Association Collaboration, searching for genetic risk factors for
ovarian cancer. These studies should provide tools to stratify
populations and provide an individualised risk assessment for
women based on their genetic make-up.
Menon U et al. Sensitivity and specificity of multimodal and ultrasound
screening for ovarian cancer, and stage distribution of detected cancers:
results of the prevalence screen of the UK Collaborative Trial of Ovarian
Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10(4):327–40.
Menon U et al. Recruitment to multicentre trials – lessons from UKCTOCS:
descriptive study. BMJ. 2008;337:a2079.
Goode EL et al. A genome-wide association study identifies susceptibility
loci for ovarian cancer at 2q31 and 8q24. Nature Genet. 2010;42(10):
874–9.
POPULATION HEALTH UCL School of Life and Medical Sciences
7
A family affair
Healing by degrees
Pregnancy and childbirth can have a significant impact
on the mental health of mothers and fathers.
Cooling of babies suffering asphyxia at birth saves lives –
and adding xenon to the mix might help even more survive.
Childbirth is supposed to be a time of great joy, but the reality
can be quite different. The stress of dealing with the needs of a
fragile new life and the accompanying upheaval, lack of sleep
and economic impact can be difficult to deal with, especially
when combined with pre-existing mental health problems.
Professor Irwin Nazareth and Dr Irene Petersen’s work on a
population cohort including new mothers and their partners
is shedding light on important issues, including parental
depression and antidepressant use in pregnancy.
The Health Improvement Network primary care database is
one of the largest of its kind in the UK, containing information
on more than 9 million patients (3.4 million active patients),
equivalent to 40 million patient years of data. Using the database
to pinpoint new mothers, Professor Nazareth’s team further
identified a male in the same household, ultimately collecting
data on 87,000 mother–father–child triads.
By the time their child was 12 years old, 39 per cent of
mothers and 21 per cent of fathers had experienced an episode
of depression, but the risk of depression was highest during the
first year after birth. The risk of postnatal depression in women
is well-known, but these data confirm that depression in fathers
is far from rare.
The database has also provided insight into the treatment
of pregnant women with depression. Although antidepressant
use increased fourfold between 1992 and 2006, pregnant
women were more likely to stop taking their medication,
particularly during the first six weeks of pregnancy. Only 10
per cent of women treated before pregnancy still received
antidepressants at the start of the third trimester, while 35 per
cent of non-pregnant women were still being treated after a
similar time period.
The difference is likely to reflect concerns about the effects
of antidepressants on an unborn child, but such risks have to be
weighed against those associated with untreated depression.
Mild cooling, ‘therapeutic hypothermia’, is now the recommended
treatment in the UK for babies suffering birth asphyxia. Its origins lie
in observations on infant brains made at UCL 30 years ago, as well
as results gained on a unique animal model still being used by Dr Nikki
Robertson and colleagues to optimise treatments. And a discovery
made at UCL more than 100 years ago may yet hold the key to further
advances.
Although used by doctors for hundreds of years, cold treatments
fell out of favour after the war. Neonatal use of cooling grew out of
studies conducted at UCL in the early 1980s by Osmund Reynolds and
colleagues, who discovered that there was a marked delay between
oxygen deprivation in infants and the ensuing neural damage. Since
then, researchers have sought ‘neuroprotective’ agents for use in this
therapeutic window – cooling being one. Babies with birth asphyxia
are now cooled by 3°C for three days.
Reynolds established a model system – the piglet – in which to study
this phenomenon and test possible neuroprotective approaches.
As well as similarities in size and physiology, the same biomarkers of
neural damage can be followed in both piglets and humans, providing
a valuable ‘bridge’ from experimental studies to clinical application.
Work on the piglet model helped to establish that mild cooling
reduces the levels of death and disability caused by birth asphyxiation.
It also helped refine treatments, identifying the optimal degree of cooling
– too much cooling and damage starts to increase again – and the
timing and duration of intervention.
Cooling was initially thought to have a generic slowing effect on
metabolism, but its effects are more subtle, influencing specific
physiological pathways and programmed cell death (apoptosis).
It may therefore be possible to enhance hypothermia’s actions by
intervening in these pathways. By a curious quirk of fate, one possible
agent is the noble gas xenon, isolated at UCL by William Ramsay in
1898. Experimental studies with xenon have been highly promising
and a clinical trial at UCLH has just begun.
Furthermore, in collaboration with the Institute of Neurology,
Dr Robertson has identified another potential neuroprotectant –
melatonin. Melatonin is a naturally occurring hormone, which influences
circadian rhythms but also has anti-ageing and anti-oxidant effects.
It too has an inhibitory effect on apoptosis and offers enhanced
protection with cooling in the piglet model, and may yet join the unusual
array of interventions for neonatal asphyxia.
Petersen I, Gilbert RE, Evans SJ, Man SL, Nazareth I. Pregnancy as
a major determinant for discontinuation of antidepressants: an analysis
of data from The Health Improvement Network. J Clin Psychiatry.
2011;72(7):979–85.
Davé S, Petersen I, Sherr L, Nazareth I. Incidence of maternal and
paternal depression in primary care: a cohort study using a primary care
database. Arch Pediatr Adolesc Med. 2010;164(11):1038-44.
Iwata O et al. “Therapeutic time window” duration decreases with increasing
severity of cerebral hypoxia-ischaemia under normothermia and delayed
hypothermia in newborn piglets. Brain Res. 2007;1154:173–80.
O’Brien FE et al. Delayed whole-body cooling to 33 or 35 degrees C and the
development of impaired energy generation consequential to transient cerebral
hypoxia-ischemia in the newborn piglet. Pediatrics. 2006;117(5):1549–59.
Kelen D, Robertson NJ. Experimental treatments for hypoxic ischaemic
encephalopathy. Early Hum Dev. 2010;86(6):369–77.
Faulkner S et al. Xenon augmented hypothermia reduces early lactate/Nacetylaspartate and cell death in perinatal asphyxia. Ann Neurol.
2011;70(1):133–50.
8
POPULATION HEALTH UCL School of Life and Medical Sciences
It should therefore be possible to arrange services
that are sex-specific and life-stage-specific, so
women can receive advice, support and services
across a range of areas that are relevant to them
at the current stage in their lives.
A key aim going forward is to
enhance service delivery, by
developing a more integrated
approach to women’s health
based on women’s needs
and wishes rather than the
boundaries of traditional
medical disciplines.
Working with partners
including the influential
‘Mumsnet’ website, Professor
Stephenson’s team is
applying this principle to
antenatal care. To support
this work, an online
‘longitudinal care record’ is
being developed to capture
information about women’s
interactions with different
parts of the health system
through their pregnancies.
Greater integration is also
the aim of a project aiming
to bring together services
linked to sexual health
and minor gynaecological
problems, which has been
well-received in initial stages.
A more general theme
is to consider women’s
health within a life-course
perspective. Women’s health
follows a well-structured
path, with reproductive
landmarks at particular life
stages (with due regard for
the fact that many women
will not have children). It
should therefore be possible
to arrange services that are
sex-specific and life-stagespecific, so women can
receive advice, support and
services across a range of
areas that are relevant to
them at the current stage in
their lives.
This idea also draws on
the life-course perspective
emphasised by cohort
studies, which have
demonstrated how health
issues important at one
stage in life might have their
roots much earlier (even
in previous generations).
It also reflects other key
themes, such as prevention
and patient-oriented service
provision, as well as the
hugely important social
inequalities agenda, through
which inequalities are
perpetuated from generation
to generation.
Highly influential work has
also been carried out at
the Institute on intersex
syndromes. For many
years, feminising surgery
was carried out on children
with ambiguous genitalia.
A review highlighting the
detrimental adult outcomes
of this practice, published
by Dr Sarah Creighton in the
Lancet, led to a complete
re-evaluation of the role
of feminising surgery in
childhood2.
As influenza virus poses a
particular threat to pregnant
women, they were a priority
group for vaccination during
the 2009 H1N1 pandemic.
A prospective cohort study,
carried out with the vaccine
manufacturers, showed
no deviation from routinely
seen outcome measures,
providing reassurance that
the pandemic flu vaccine
was safe for use in this
important group3.
Screening and detection
Primary care
The reproductive health of
women and health of infants
is also studied in other areas
of UCL. Analysis of health
records can be an important
way of gathering information
about pregnancy, childbirth
and infant care. Linking
health records to household
arrangements, for example,
has provided insight about
antidepressant and antibiotic
use by mothers and a
surprisingly high incidence
of paternal depression (see
page 8).
Primary care researchers at
UCL, led by Professor Irwin
Nazareth, were selected to
explore the safety of H1N1
swine flu vaccination in
pregnant women.
Research at the UCL
Institute of Child Health
naturally also impinges on
maternal and infant health.
Several population-based
studies have addressed
early detection of potentially
hazardous infections or
inherited conditions.
In a study comparing
countries across Europe,
Professor Ruth Gilbert
and colleagues found
that identifying the singlecelled parasite Toxoplasma
in pregnant women, and
treating infections with
antibiotics, could reduce
serious neurological effects
or death in infected offspring
by about three-quarters4.
However, there was no
evidence that prenatal
2 Creighton SM, Minto CL, Steele SJ.
Objective cosmetic and anatomical
outcomes at adolescence of feminising
surgery for ambiguous genitalia done
in childhood. Lancet. 2001;358(9276):
124–5.
3 Tavares F et al. Pregnancy and safety
outcomes in women vaccinated with
an AS03-adjuvanted split virion H1N1
(2009) pandemic influenza vaccine
during pregnancy: A prospective cohort
study. Vaccine. 2011;29(37):6358–65.
4 Cortina-Borja M et al. Prenatal
treatment for serious neurological
sequelae of congenital toxoplasmosis:
an observational prospective cohort
study. PLoS Med. 2010;7(10). pii:
e1000351.
POPULATION HEALTH UCL School of Life and Medical Sciences
9
treatment significantly
reduced the risk of fetal
infection. Toxoplasma
infection can lead to
neurological damage and
to eye disease in infected
fetuses. However, infections
are relatively rare and a
randomised controlled trial
and economic analysis
would be needed before a
screening policy could be
considered in the UK or other
low-prevalence countries.
The study also found that
a less potent antibiotic,
spiramycin, was as good
as the more commonly
used, and more toxic,
pyrimethamine-sulfonamide.
A pilot study led by
Professor Carol Dezateux
has led to the introduction
of a blood test for a rare
metabolic condition –
medium chain acyl CoA
dehydrogenase deficiency
(MCADD) – for all newborn
babies across England.
MCADD affects the body’s
ability to break down fat for
energy, and can be fatal
unless treated.
10
The pilot study, at six
centres, tested 1.5 million
babies over four years.
Around 200 tested positive
and about 150 were
confirmed as having MCADD
through further tests. As well
as confirming that MCADD
detection was technically
feasible, the pilot also
showed that the relatively
small number of cases could
be identified without causing
anxiety to the families of the
vast majority of unaffected
children. The test is also
practicable, as it can be
applied to routinely taken
blood spots.
In other work, Professor
Bobby Gaspar and
colleagues have identified
significant benefits
associated with detection
of severe combined
immunodeficiency at birth5.
By comparing patients
and their younger siblings
who were diagnosed at
birth, the UCL team found
that the latter suffered
fewer infections and had
dramatically better survival
both before and after bone
marrow transplant. These
findings, and other evidence,
form a strong case for
newborn screening of all
infants for severe combined
immunodeficiency.
Observational studies are
also being used to explore
issues related to pregnancy
and childbirth. Dr Claire
Townsend and colleagues
have looked at the impact of
antiretroviral drugs on HIVinfected pregnant women.
The drugs have dramatically
cut the incidence of motherto-child transmission of the
virus, and do not appear to
cause fetal abnormalities,
but may be associated
with an increased risk of
premature delivery 6.
Other trials are examining
interventions to achieve
healthier pregnancies.
Dr Nick Greene and
colleagues, for example,
are testing whether a simple
nutritional supplement,
inositol, can reduce the
POPULATION HEALTH UCL School of Life and Medical Sciences
incidence of neural tube
defects. The trial builds
on work in mice showing
that inositol can prevent
neural tube defects that do
not respond to folate, the
supplement usually given
to prevent such defects.
Dietary supplements are
also a research interest
of Dr Elina Hypönnen.
She has drawn attention
to the conflicting policy
advice currently surrounding
the use of vitamin D
supplements in women
of child-bearing age
(see page 11).
5 Brown L et al. Neonatal diagnosis of
severe combined immunodeficiency
leads to significantly improved survival
outcome: the case for newborn screening. Blood. 2011;117(11):3243–6.
6 Townsend CL, Tookey PA, Newell ML,
Cortina-Borja M. Antiretroviral therapy in
pregnancy: balancing the risk of preterm
delivery with prevention of mother-tochild HIV transmission. Antivir Ther.
2010;15(5):775–83.
Townsend CL, Willey BA, Cortina-Borja
M, Peckham CS, Tookey PA. Antiretroviral therapy and congenital abnormalities
in infants born to HIV-infected women in
the UK and Ireland, 1990-2007. AIDS.
2009;23(4):519–24.
A well-conceived plan?
D for deficiency
An evaluation of the UK’s teenage pregnancy strategy
suggests it may have had some impact, but may not have
been tackling all the right risk factors.
Is vitamin D deficiency widespread in the UK?
Wilkinson P et al. Teenage conceptions, abortions, and births in England,
1994-2003, and the national teenage pregnancy strategy. Lancet.
2006;368(9550):1879–86.
For more than 150 years sunshine and cod liver oil have been known
to prevent rickets in children. The discovery of vitamin D provided
a mechanistic explanation for their effects. But with rickets beginning
to reappear in the UK, and vitamin D implicated in a far wider range
of physiological processes, Dr Elina Hyppönen suggests that vitamin
D deficiency is again a public health issue.
The wider impact of vitamin D was amply demonstrated in a study
of more than 12,000 pregnant women in north Finland, who were
enrolled in a birth cohort in 1966. Many (but not all) of the infants
received vitamin D supplements, most at very high doses, providing
a ‘natural experiment’ in which to study the effects of supplementation
on later health.
With colleagues in Finland, Dr Hyppönen found a strong inverse
relationship between vitamin D intake and type 1 diabetes,
suggesting that it may be protecting against development of this
autoimmune disease. The population findings tallied with a growing
awareness that vitamin D had a potent effect on immune responses.
Vitamin D also has an important role in pregnancy, severe
deficiency causing potentially life-threatening neonatal complications.
But evidence is growing that less serious deficiency may have
implications for the health of mother and child.
Because of the UK’s climate, and reduced exposure to sunlight
because of skin cancer concerns, vitamin D synthesis in the skin
is limited. Work on the 1958 British Birth Cohort (see page 26), for
example, found alarmingly high levels of deficiency, particularly in
winter and spring.
Unfortunately, Dr Hyppönen points out, the UK has a contradictory
policy framework that is sending confusing messages about the
need for vitamin D. Official Department of Health advice to healthy
pregnant and breastfeeding mothers is to ensure they are getting
adequate vitamin D; however, these recommendations are not
systematically endorsed by NICE. The UK is also unique among 31
European countries in not having any recommendation for dietary
vitamin D intake for the general adult population.
While attempting to clarify this policy confusion, Dr Hyppönen has
also turned to genetics to unpick the physiology of vitamin D. Her
work as part of the SUNLIGHT consortium has identified four genes
influencing vitamin D status (and susceptibility to type 1 diabetes).
Currently Dr Hyppönen leads a large international collaboration aiming
to establish the wider effects of vitamin D deficiency using genes as
proxy markers for low vitamin D levels.
Allen E et al. Does the UK government’s teenage pregnancy strategy deal
with the correct risk factors? Findings from a secondary analysis of data
from a randomised trial of sex education and their implications for policy.
J Epidemiol Community Health. 2007;61(1):20–7.
Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake
of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet.
2001;358(9292):1500–3.
The UK has traditionally topped the table for teenage pregnancy
rates in west European countries. In 1999, in what was widely
seen as a significant shift from morally led to evidence-driven
policy development, the UK Government introduced a national
teenage pregnancy strategy with very ambitious targets –
to halve teenage pregnancies by 2010. A mid-term evaluation
by Professor Judith Stephenson and colleagues found some
progress being made toward this target and provided a more
refined view of key risk factors.
The 1999 strategy was notable in focusing on the risk factors
associated with teenage pregnancy – such as socioeconomic
disadvantage, being the child of a teenage parent, not being in
education or work, alcohol misuse, and low levels of sexual health.
However, the evidence it drew upon was limited and relatively
old. The evaluation therefore looked both at how successful it
had been and whether its priority areas were still appropriate.
The conception data revealed that teenage pregnancies
did decline from 1999 onwards, by about 2 per cent a year
or 11 per cent total up to 2004. Although encouraging, the
decline would not enable the 50 per cent target to be reached.
One notable finding was that the biggest effects were seen
in socioeconomically deprived areas – the opposite of what
is usually seen in population interventions – suggesting that
targeting such areas was effective.
As for the key risk factors, the analysis confirmed many of the
previously identified factors, particularly socioeconomic status,
low educational attainment and expectations. Several factors
appeared to be protective, including easy communication with
parents and guardians and obtaining information about sex
at school. However, sexual knowledge per se did not seem
to be a significant risk factor – although myths can still arise,
the basics of sex and pregnancy are now much more widely
known by teenagers. Hence it may be that development of open
communication and emotional literacy in sex education may be
the route to further reductions in teenage pregnancies.
Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y:
nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr.
2007;85(3):860–8.
Hyppönen E, Boucher BJ. Avoidance of vitamin D deficiency in pregnancy
in the United Kingdom: the case for a unified approach in National policy.
Br J Nutr. 2010;104(3):309–14.
Wang TJ et al. Common genetic determinants of vitamin D insufficiency:
a genome-wide association study. Lancet. 2010;376(9736):180–8.
POPULATION HEALTH UCL School of Life and Medical Sciences
11
The first National Survey of Sexual Attitudes and Lifestyles,
Natsal, was a groundbreaking project documenting the
sexual behaviours of the British population. Now in its third
incarnation, Natsal provides a fascinating insight into this
most private of areas but, more importantly, also generates
invaluable evidence shaping health and social policy.
Let’s talk about sex
In 1981, a frightening new
health threat appeared:
HIV and AIDS. First noted
in an obscure report of an
unusual immunodeficiency
affecting the San Francisco
gay community, AIDS
rapidly mushroomed into
a global crisis. In an age
before antiretroviral drugs,
HIV infection was a death
sentence, and there was
a strong public health
imperative to prevent its
spread.
But as well as limited
knowledge about the virus
itself, the UK’s public health
authorities had almost no
evidence on which to base
public health campaigns.
Almost nothing was known
about behaviours relevant
to sexual health, and
attitudes that might affect
them. Although some data
did exist, they were drawn
largely from sexual health
clinics, and their relevance
to general populations was
debatable.
This glaring gap was an
important stimulus for
a uniquely ambitious
project: a large, nationally
representative survey
of sexual attitudes and
lifestyles. Its aim would
be to gather information
to inform public health
measures – for HIV/
AIDS and other sexually
transmitted infections – and
other areas of importance to
health or social policy, such
12
“I remember saying one day, ‘we really
ought to do a general population-based
study on sexual behaviour with a proper
random sample’. I remember a senior
colleague… looking at me with an
expression that suggested
I’d cracked.”
Anne Johnson
as age at first intercourse
and first pregnancy.
The plans for Natsal were
hatched by Professor
Anne Johnson at UCL,
in collaboration with
colleagues now at the
London School of Hygiene
and Tropical Medicine and
the National Centre for
Social Research. They were
almost scuppered when the
Conservative Government
– at the personal behest of
Prime Minister Margaret
Thatcher – vetoed the study,
arguing that it was too
intrusive, even though the
science had been favourably
reviewed by Research
Councils. Fortunately, the
Wellcome Trust stepped in
with funding enabling the
first survey, Natsal I, to go
ahead in 1990. Attitudes had
relaxed sufficiently a decade
later for the MRC to be able
to fund a follow up, Natsal II,
completed in 2001. A third
survey, funded by the MRC
and the Wellcome Trust,
is due to report in 2013.
Natsal I provided a valuable
snapshot to inform the
response to the HIV
epidemic. Natsal II was
important not only in
providing an updated data
set but also in giving insight
into behavioural trends.
And the period between
1990 and 2000 was one of
considerable social change.
Following the HIV scare
in the 1980s, sexual risk
behaviours had reduced
and STI rates declined
rapidly. Between 1990 and
2000, however, those trends
began to reverse. Both
men and women reported
more sexual partners
(consistent with the steep
rise in sexually transmitted
infections from 1995
onwards). And although
condom use had increased,
Natsal II identified major
changes in a range of
risky behaviours, including
increased numbers of
heterosexual partners,
homosexual encounters,
concurrent partnerships,
paying for sex and
heterosexual anal sex.
Natsal II also revealed a
continuing drop in the age
POPULATION HEALTH UCL School of Life and Medical Sciences
Ethnic variation
Sexual behaviour varies in different
ethnic populations.
By sampling across different ethnic groups
in Britain, Natsal has been able to shed light
on sexual behaviours and attitudes within
particular populations. Indeed, reported
behaviours differed markedly between groups.
In terms of numbers of sexual partners, for
example, black Caribbean and black African
men reported higher numbers of lifetime sexual partners (median nine), as did
white and black Caribbean women (median five and four, respectively). Indian and
Pakistani men and women typically reported fewer partners (as well as later age of
first intercourse). These figures were mirrored in the incidence of STIs.
Although individual risk behaviours are the biggest determinant of the likelihood
of sexual health problems, population norms will also have an influence – people
cannot entirely avoid what is happening around them.
The results provide important insight into the sexual health issues of ethnically
defined subpopulations. They should provide the backdrop against which culturally
sensitive interventions can be developed.
Fenton KA et al. Ethnic variations in sexual behaviour in Great Britain and risk of sexually
transmitted infections: a probability survey. Lancet. 2005;365(9466):1246–55.
of first intercourse – 30 per
cent of men and 26 per
cent of women aged 16–19
reported having sex before
the age of 16. However,
the trend for women to
have sex at younger ages
appeared to be stabilising
by mid-decade. Early
intercourse was associated
with poorer later life sexual
health, and was linked to
early onset of menstruation,
disrupted family life and, in
particular, poor educational
achievement – emphasising
the important links between
social and health policy.
Natsal II also offered testing
for Chlamydia to half the
population of sexually
active 18–44-year-olds.
Surprisingly, Chlamydia
was as prevalent in men
than women, even though
national screening initiatives
had previously targeted
women.
Natsal data have been
a treasure trove for
researchers exploring
important sexual health
issues, and form the
widely used benchmark
against which other studies
compare their findings.
Natsal III is an even bigger
exercise, recruiting 15,000
men and women aged 16–74
– the first time people aged
60–74 have been included.
It will cover similar ground
to its predecessors, to
enable comparisons to be
made, while incorporating
methodological advances,
some new areas and
biological measures (STIs
and sex hormone levels).
A combination of data
from all three studies will
provide extraordinary
power to examine not just
representatives of different
age groups over time, but
also the experience of
successive birth cohorts,
as data will be available on
people born between the
1930s and the 1990s.
Johnson AM et al. Sexual behaviour
in Britain: partnerships, practices,
and HIV risk behaviours. Lancet.
2001;358(9296):1835–42.
Wellings K et al. Sexual
behaviour in Britain: early
heterosexual experience. Lancet.
2001;358(9296):1843–50.
Fenton KA et al. Sexual behaviour in
Britain: reported sexually transmitted
infections and prevalent genital
Chlamydia trachomatis infection.
Lancet. 2001;358(9296):1851–4.
Asking for help
Natsal revealed that sexual function
problems were surprisingly common, but
relatively few people seek specialist help.
One area touched upon in the Natsal survey
was the extent of sexual function problems in
the population at large. Defined quite broadly
– having at least one sexual problem lasting
at least one month – sexual function problems
were remarkably common, reported by 35 per
cent of men and 54 per cent of women.
For men, the most common problems were
lack of interest in sex, premature ejaculation
and anxiety; for women, inability to achieve
orgasm and painful intercourse. Persistent
sexual problems – of at least six months’
duration – were less common but by no means
rare, affecting 6.2 per cent of men and 15.6 per
cent of women.
Notably, just 11 per cent of men and 21 per
cent of women who reported sexual function
problems had actually sought help for their
problem. Even among the smaller number with
persistent problems, the numbers were only
21 per cent and 32 per cent.
The nature of ‘sexual dysfunction’, and
the role of medical interventions, remains
a controversial area. Nevertheless, Natsal
provided valuable evidence on what has been
a ‘hidden’ issue.
Mercer CH et al. Sexual function problems and help
seeking behaviour in Britain: national probability
sample survey. BMJ. 2003;327(7412):426–7.
POPULATION HEALTH UCL School of Life and Medical Sciences
13
SECTION 2
Young people
and transition
to adulthood
A succession of birth cohorts has shed light
on the health, development and welfare of
generations of UK children. Much has changed
for the better, but new issues have emerged –
not least high levels of obesity – and inequality
remains a powerful force affecting young people
and the adults they become.
14
POPULATION HEALTH UCL School of Life and Medical Sciences
Improved nutrition and living
conditions, education and
the control of infectious
disease, most recently
by vaccination, have had
a profound impact on
young people’s health.
Comparisons across UK
birth cohorts – those of 1946,
1958, 1970 and 2000 – have
shown how childhood has
changed, in terms of health
and physical, social and
educational development.
Indeed, while there is no
cause to be complacent,
a major focus of research
in young people is the
longer-term consequences
of childhood experiences.
A life-course perspective
on health – a particularly
valuable aspect of long-term
cohort studies, particularly
‘cradle-to-grave’ studies
such as the 1946 Birth
Cohort (see page 38) –
can reveal how early
influences affect later-life
illness. It is increasingly
apparent that experiences
at school age (and even
earlier) can have a profound
effect on later-life physical
and mental well-being.
...experiences at school age (and even earlier)
can have a profound effect on later-life physical
and mental well-being.
In this context, the rise
in childhood obesity
documented in the
Millennium Birth Cohort
is of some concern (see
page 16). By the age of
three, nearly one in four
UK children were classified
as overweight or obese,
and in some populations
the proportion was even
higher. An analysis of
trends suggests that those
overweight early in life –
as young as three years
old – tend to be the same
children who are overweight
at later ages. As well as
the immediate impacts of
obesity on quality of life
(and interactions with peers),
excess weight gain in early
years is storing up a host
of problems for later life.
Obesity will be a major focus
of the latest UK birth cohort,
to be launched in 2012.
The £28 million initiative,
funded by the UK’s Medical
Research Council (MRC)
and Economic and Social
Research Council, is being
led by Professor Carol
Dezateux, Director of the
MRC Centre of Epidemiology
for Child Health at UCL,
who chairs the Child Health
Group of the Millennium
Cohort Study.
The 2012 Birth Cohort will
address important questions
affecting children’s health
and well-being, from
the key factors enabling
children to overcome social
disadvantage at birth to
links between eating and
physical activity behaviours
in very early life and
growth and weight gain in
later childhood. It will also
focus on temperament
and social and emotional
communication styles,
as well as the effects of
exposure to a range of
environmental pollutants
during early infancy.
POPULATION HEALTH UCL School of Life and Medical Sciences
15
Weighty matters
Special cases
Unhealthy weight gain starts remarkably early in life, work
on the Millennium Birth Cohort suggests.
Treatment of HIV in the young requires special consideration.
The UK’s ‘obesity epidemic’ raises fears of a surge in chronic later
life diseases such as type 2 diabetes. Alarmingly, excess weight
gain is already apparent in young people, triggering a range of
public health promotions to promote healthier lifestyles, such
as the ‘Change4Life’ campaign. The work of Professors Carol
Dezateux, Catherine Law, Tim Cole and their colleagues Lucy
Griffiths and Summer Hawkins on the Millennium Birth Cohort
has revealed worrying levels of obesity at early ages and shed
important light on its origins.
Data from the Millennium Birth Cohort has revealed the full
scale of unhealthy weight gain in infancy and childhood. By age
three, almost one in four children (23 per cent) were classified as
overweight or obese. A variety of factors were associated with
excess weight – mothers smoking during pregnancy, parents
being overweight, mothers being overweight before pregnancy
and maternal working. Black children were at particular risk,
while breastfeeding and Indian ethnicity were associated with
protection from excess weight.
Obesity levels were similar at age five. Indeed, the trajectory of
weight gain seems to have been set early in life, with 63 per cent
of overweight children and 88 per cent of obese children showing
rapid weight gain between the ages of three and five. As well as
high BMI at age three, key influences were very similar to those
seen before, plus exposure to second-hand smoke.
The numbers stress how early childhood obesity arises, and the
likelihood that those overweight at an early age are likely to stay
overweight. They also highlight significant modifiable parental
influences – particularly smoking and weight. Some 28 per cent of
mothers were overweight or obese before pregnancy and 34 per
cent smoked during pregnancy. More positively, breastfeeding
helped prevent excess weight gain before age three.
The long-term risks of being overweight are well-established,
but the Millennium Birth Cohort has also highlighted its immediate
psychosocial impacts. At age five, obese boys were at higher risk
of conduct problems, hyperactivity and attention difficulties, and
peer relationship problems; girls were at risk only for the last of
these. Thus obese children – and boys in particular – are at risk of
emotional and behavioural problems at a very young age.
Hawkins SS et al. An ecological systems approach to examining risk
factors for early childhood overweight: findings from the UK Millennium
Cohort Study. J Epidemiol Community Health. 2009;63(2):147–55.
Griffiths LJ et al. Risk factors for rapid weight gain in preschool
children: findings from a UK-wide prospective study. Int J Obes (Lond).
2010;34(4):624–32.
Griffiths LJ, Smeeth L, Hawkins SS, Cole TJ, Dezateux C. Effects of
infant feeding practice on weight gain from birth to 3 years. Arch Dis Child.
2009;94(8):577–82.
Griffiths LJ, Dezateux C, Hill A. Is obesity associated with emotional and
behavioural problems in children? Findings from the Millennium Cohort
Study. Int J Pediatr Obes. 2011;6(2-2):e423–32.
16
Although HIV is predominantly a sexually transmitted infection, it can
also be acquired by infants in the womb or by breastfeeding. Professor
Diana Gibb and colleagues at the MRC Clinical Trials Unit have
contributed to a series of influential international collaborations that
have shaped WHO treatment guidelines for paediatric HIV worldwide.
Although antiretrovirals have proven spectacularly successful in
combating HIV, they are not a cure and treatment will be lifelong.
They have both short-term and long-term side-effects, and their use
raises the risk of drug resistance. Young people’s immune systems
are also more dynamic than those of adults, so potentially more able
to generate new immune cells. Deciding when to start treatment
therefore calls for careful weighing up of pros and cons.
For infants, recent evidence has been unequivocal – infants
should be started on antiretrovirals as rapidly as possible. Key data
have come from the CHER trial, a collaboration between the MRC
Clinical Trials Unit and groups in South Africa, which showed a
fourfold reduction in death rates when infants were tested and treated
immediately, rather than waiting for clinical symptoms to develop
or for CD4 cell numbers to fall significantly. Although this trial was
carried out in South Africa, results have also changed European
and US guidelines; a meta-analysis of data from European infants
confirmed a similar benefit in European settings.
For children above the age of one, data from multiple studies
suggest that treatment should begin when certain clinical signs
appear or when CD4 cell numbers fall below threshold levels.
A series of clinical trials and cohort studies run by the MRC Clinical
Trials Unit in collaboration with the French ANRS trials unit under the
PENTA (Paediatric European Network for Treatment of AIDS) umbrella
has contributed much to inform the best management strategies
for HIV-infected children, including practical issues such as which
antiretrovirals to start and switch to, what doses to use and when to
change drugs when first-line treatment starts to fail.
Concerns about drug resistance were highlighted in a recent metaanalysis of children’s cohorts, which demonstrated higher levels of
resistance five years after starting treatment than in adults.
Violari A et al. Early antiretroviral therapy and mortality among HIV-infected
infants. N Engl J Med. 2008;359:2233–44.
Goetghebuer T et al. Effect of early antiretroviral therapy on the risk of AIDS/
death in HIV-infected infants. AIDS. 2009;23:597–604.
Dunn D et al. HIV Paediatric Prognostic Markers Collaborative Study Group.
Short-term risk of disease progression in HIV-1-infected children receiving no
antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet.
2003;362(9396):1605–11.
PENPACT-1 (PENTA 9/PACTG 390) Study Team et al. First-line antiretroviral
therapy with a protease inhibitor versus non-nucleoside reverse transcriptase
inhibitor and switch at higher versus low viral load in HIV-infected children: an
open-label, randomised phase 2/3 trial. Lancet Infect Dis. 2011;11(4):273–83.
Pursuing Later Treatment Options II (PLATO II) project team for the
Collaboration of Observational HIV Epidemiological Research Europe
(COHERE) et al. Risk of triple-class virological failure in children with HIV:
a retrospective cohort study. Lancet. 2011;377(9777):1580–7.
POPULATION HEALTH UCL School of Life and Medical Sciences
As well as documenting trends in nutrition,
exercise and weight gain, the cohort has also
shed light on issues such as uptake of the
MMR vaccine and the interplay between work,
parenting and child development.
The pioneering 1946 Birth
Cohort was established
because of concerns about
the impact of poverty and
poor living conditions
on childbirth, and has
generated much information
about the impact of social
inequalities on health
and social development.
Despite the 65-year gap,
these issues remain equally
pertinent today. Though
health inequalities are now
widely recognised, they
remain stubbornly large.
Early years are crucial in
establishing the trajectory
for later life, and will be a
particular focus of the new
cohort. There will also be
an opportunity to explore
how biological, social and
other environmental factors
interact during this critical
period to shape current and
future health and well-being.
Work on the new cohort is
likely to feed into health and
social policy, mirroring the
impact of the Millennium
Birth Cohort. As well as
documenting trends in
nutrition, exercise and weight
gain, the cohort has also
shed light on issues such as
uptake of the MMR vaccine
and the interplay between
work, parenting and child
development. Indeed, one of
the strengths of the cohorts
is their holistic approach,
drawing out links between
social, educational and
health domains.
Insight into obesity in
children has also come from
other work on cohorts being
studied at UCL. Professor
Jane Wardle has carried out
multiple studies investigating
children’s food choices.
These include the PEACHES
(Physical Exercise and
Appetite in Children) study,
a longitudinal investigation
of behaviours affecting
obesity risk in 7–8-yearold children, TEMPEST, an
EU-funded study of the role
of self-regulatory skills in
adolescents, and the GEMINI
Twin Birth Cohort, 2402
families with twins in England
and Wales born between
March and December 2007.
Professor Wardle is
particularly interested in
the links between genetic
factors implicated in weight
gain and eating behaviours.
The studies recognise that
childhood weight depends
on the interplay between
many factors – including
genetics, parenting practice
and the home environment.
Her group has also run
several interventions aimed
at improving young people’s
diets. These include the
POPPETS ‘Healthy Habits’
(POSH) intervention, which
uses the habit-formation
framework to modify parental
behaviour in order to improve
children’s diets, as well as
a family-based intervention
for childhood obesity, run
in partnership with Great
Ormond Street Hospital. This
work is carried out through
the Weight Concern charity
established by Professor
Wardle. Her group has also
tested the impact of reward
on children’s eating habits7.
Other UCL researchers
are also examining the
experience and care of
overweight children, but
with a greater focus on
implications for the NHS.
Professor Russell Viner
has been awarded major
funding from the National
Institute for Health Research
(NIHR) for five linked studies
where significant gaps
in knowledge have been
identified. These include
pilot studies of an electronic
tool to guide referrals, a trial
of the Healthy Eating and
Lifestyle Programme (HELP),
an evaluation of the use of
anti-obesity drugs in young
people, and an assessment
of bariatric surgery in
adolescents.
The health and well-being
of children living with HIV
needs special attention.
Pan-European cohort
studies, organised by the
MRC Clinical Trials Unit,
have provided information
about key issues such as
which drugs to use and
when to start antiretroviral
treatment (see page 16).
As the first children infected
with HIV reach adolescence
and enter adulthood, further
work will be needed to
support them through a
difficult period in life and to
help them manage what is in
effect a chronic condition.
7 Cooke LJ et al. Eating for pleasure
or profit: the effect of incentives on
children’s enjoyment of vegetables.
Psychol Sci. 2011;22(2):190–6.
POPULATION HEALTH UCL School of Life and Medical Sciences
17
A programme of research on public attitudes
to the human papilloma virus vaccine, led by
Professor Wardle, helped to shape its national
rollout.
Vaccination
Vaccines have been an
essential component of
public health, and UCL
research has provided
significant input into
important areas of vaccine
policy. A programme of
research on public attitudes
to the human papilloma virus
vaccine, led by Professor
Wardle, helped to shape its
national rollout.
The Millennium Birth Cohort
provided an opportunity to
examine take up of MMR
and use of single antigen
vaccines8. Uptake was high
(89 per cent) but below
that required for effective
herd immunity. Use of
single antigen vaccines was
associated with wealthier,
more educated families –
a rare example of a ‘reverse
socioeconomic gradient’.
Worryingly, almost half
of children given single
vaccines did not receive
all three jabs.
Sexual behaviours
One of the potentially most
important influences on
health from adolescence
onwards is sexual behaviour.
Here, the National Survey
18
of Sexual Attitudes and
Lifestyles (Natsal), led by
Professor Anne Johnson
(see page 12), has provided
valuable insight into
behaviours likely to affect
the spread of sexually
transmitted infections
(STIs), including HIV. The
world’s first representative
population surveys of sexual
attitudes and lifestyles,
Natsal revealed significant
increases in risk-taking
behaviour and in STIs in
young adults between its
surveys in 1990 and 2000.
Natsal 2000 data revealed
a marked shift in the age
at which people were first
having sex – 30 per cent
of men and 26 per cent of
women reported having sex
before the age of 16. The
third and most extensive
survey, Natsal III, due to
report in 2013, will reveal
whether these trends are
continuing.
Natsal provided information
on attitudes and behaviours
within different ethnic
communities, and other UCL
research has generated
important findings about
risk behaviours of migrant
groups. Dr Fiona Burns
and colleagues have shown
that more African men than
previously suspected had
acquired HIV in the UK. More
recently, her work has shed
important light on the risk
behaviours of East European
migrants (see page 19).
Mental health
UCL’s Priment Clinical
Trials Unit is coordinating
several studies relevant to
children and young adults.
These include the HELP trial
of obesity management in
children and several studies
linked to care of people with
schizophrenia (including the
innovative MATISSE trial of
art therapy).
Other projects are examining
the care of people with
schizophrenia or other
long-term mental conditions.
In the REACT project, for
example, Dr Helen Killaspy
and colleagues found that,
in the UK setting, assertive
community care was no
better than care provided
by community mental health
teams9 (work that led to an
Association of European
Psychiatrists’ research
prize in 2007). Dr Killaspy
has also led an EC-funded
programme developing a
toolkit for assessment of
long-term care facilities.
UCL researchers are also
involved in major intervention
projects aimed at the mental
POPULATION HEALTH UCL School of Life and Medical Sciences
health and well-being of
young people. Professor
Peter Fonagy is leading the
START (Systemic Therapy
For At Risk Teens) trial,
a large multicentre study
spread across 10 sites
in the UK investigating
an intervention for young
people and their families
who are experiencing
difficulties at home, at
school and possibly with the
police. He is also involved
in the IMPACT study, a
randomised controlled trial
of two psychotherapies in
adolescents with moderate
to severe depression. His
group is also evaluating the
Targeted Mental Health in
Schools (TaMHS) initiative,
a three-year programme
providing mental health
support in schools for
children aged five to
13 at risk of, or already
experiencing, mental health
problems.
8 Pearce A et al. Factors associated
with uptake of measles, mumps, and
rubella vaccine (MMR) and use of single
antigen vaccines in a contemporary UK
cohort: prospective cohort study. BMJ.
2008;336(7647):754–7.
9 Killaspy H et al. Randomised evaluation of assertive community treatment:
3-year outcomes. Br J Psychiatry.
2009;195(1):81–2.
Supporting modern families
Risky behaviours?
An increase in the numbers of working mothers may
impact on children’s health?
The first major survey of Central and East European
migrants to London has revealed concerning risk-taking
behaviours.
A notable social trend of recent decades has been the increasing
numbers of women in paid work, a trend that is unlikely to be
reversed. Yet, as research by Professor Catherine Law and
colleagues on the Millennium Birth Cohort indicates, these
changes may also have knock-on effects, both good and bad,
on children’s health.
One significant area of inquiry has been children’s diet and
activity habits. After adjustment for other influences on children’s
health behaviours (such as mother’s level of education), at age
five, children of employed mothers were more likely to consume
sweetened drinks between meals and less likely to snack on fruit
or vegetables. They were also more likely to spend two hours or
more in front of the TV or computer and more likely to be driven
to school than children whose mothers did not go out to work.
Consistent with these changes, maternal employment after birth
was associated with early childhood overweight, independent of
other factors such as social circumstances. Strikingly, though, this
was true only for children from high-income households. Hence it
may be lack of time rather than money that underlies this greater
risk of obesity.
The increase in women working has depended on a growth
in childcare, either formal or informal (such as family members).
Not surprisingly, early return to employment after birth and use
of day care is also associated with lower rates of breastfeeding.
Interestingly, while formal childcare had no independent link
with early childhood overweight, informal childcare did – but
only among the better off. It may therefore make sense to target
health promotion at grandparents, a frequent source of informal
childcare.
Use of both formal and informal childcare also had a negative
effect on breastfeeding, an area where the UK has a poor record.
In informal care, all groups of mothers were affected, but in formal
childcare the effect was seen only in better off families.
Collectively the results reveal that women’s greater participation
in the workplace has the potential to affect their children’s health.
They highlight areas in which social policies can be focused
to help modern families, in their many forms, provide a healthy
environment for their children.
Hawkins SS, Cole TJ, Law C. Maternal employment and early childhood
overweight: findings from the UK Millennium Cohort Study. Int J Obes
(Lond). 2008;32(1):30–8.
Hawkins SS et al. Examining the relationship between maternal
employment and health behaviours in 5-year-old British children.
J Epidemiol Community Health. 2009;63(12):999–1004.
Pearce A et al. Is childcare associated with the risk of overweight and
obesity in the early years? Findings from the UK Millennium Cohort Study.
Int J Obes (Lond). 2010;34(7):1160–8.
Pearce A et al. Childcare use and inequalities in breastfeeding: findings
from the UK Millennium Cohort Study. Arch Dis Child. 2010 Jun 7.
The accession of ten Central and East European countries into the
EU since 2004 has led to extensive migration to the UK. Improving the
health of migrants should benefit the UK and their home countries, so
it is important to get a good picture of their health-related behaviours
and needs. The SALLEE (Sexual Attitudes and Lifestyles of London’s
Eastern Europeans) project, run by Dr Fiona Burns and colleagues,
including researchers at UCL’s School of Slavonic and East European
Studies, has provided the first detailed information about these
behaviours, and identified several of public health concern.
Capturing a population sample broadly representative of Central
and East European migrants proved a major challenge. Various
sampling strategies were adopted, including community sampling
in two London boroughs, Newham and Hammersmith, surveying
attendees at sexual and reproductive health clinics, and via the
internet, including two gay dating websites. In all the team recruited
3638 migrants, including 691 men who have sex with men and 299
clinic attendees. Results were compared with UK population data.
Of particular note, heterosexual migrants reported high rates of
behaviours associated with increased risk of HIV infection or sexually
transmitted infection (STI), such as having multiple partners, injecting
drug use, or paying for sex – something a third of males reported.
STI rates in these Central and Eastern European migrants were lower
than those seen in London populations, but the behaviours reported
after arrival may place them at increased risk of STIs in the UK.
Similarly, the gay men reported high-risk behaviours. Nearly a
quarter reported unprotected anal intercourse with a casual partner
in the past year and 20 per cent had been paid for sex at some
time in their lives. The UK has Western Europe’s highest rate of HIV
infection, and it again appears that migrants are adopting the risky
behaviours prevalent locally – possibly a reaction to the limited
opportunities available back home, where homosexuality is generally
still stigmatised.
Economic migrants are typically adventurous, willing to take the
risk of moving countries to better themselves. These results suggest
that risk-taking might also extend to their lifestyles. With many UK
and European nationals making the most of economic opportunities
throughout the EU, the results not only provide important food for
thought for UK public health authorities but also emphasise the need
for healthcare and disease surveillance systems to transcend national
boundaries.
Burns FM et al. Sexual and HIV risk behaviour in Central and Eastern European
migrants in London. Sex Transm Infect. 2011;87(4):318–24.
Evans AR et al. Factors associated with genitourinary medicine clinic
attendance and sexually transmitted infection diagnosis among central and
east European migrants in London. Sex Transm Infect. 2011;87(4):331–6.
Evans AR et al. Central and East European migrant men who have sex
with men: an exploration of sexual risk in the UK. Sex Transm Infect.
2011;87(4):325–30.
POPULATION HEALTH UCL School of Life and Medical Sciences
19
SECTION 3
The middle years
Our middle years are often when our lifestyle
catches up with us. The first signs begin to appear
of the common conditions that are responsible
for the bulk of deaths in the UK. Health priorities
therefore span not just immediate treatments but
ways to preserve good health in later life.
20
POPULATION HEALTH UCL School of Life and Medical Sciences
The middle years are
a period when we are
accumulating experiences
that will shape our future
health. Whether we are
careful with our diet and
exercise will influence
our risk of heart disease;
whether we can maintain a
healthy weight will affect our
risk of type 2 diabetes; our
sunbathing behaviours will
impact on our risk of skin
cancer; if we smoke, we are
increasing our chances
of suffering a wide range
of conditions.
Thus as well as endeavouring
to stay healthy in the present,
the middle years are also
about taking positive action
to remain healthy in the
future – the kind of ‘delayed
gratification’ at which
humans are notoriously bad.
Consistent with this idea
is a growing emphasis on
identifying the early signs
of disease, to promote
prevention and early
treatment.
Cohort studies are
particularly well-suited
to identifying temporal
associations. The cohorts
The cohorts studied by UCL researchers have
provided important information about life-course
influences on adult-onset diseases, particularly
the ‘lifestyle’-associated conditions affecting the
heart, circulatory system and metabolism.
studied by UCL researchers
have provided a wealth
of important information
about life-course influences
on adult-onset diseases,
particularly the ‘lifestyle’associated conditions
affecting the heart,
circulatory system
and metabolism.
Among the most notable
has been the Whitehall
study. Set up in 1967 by
Professor Geoffrey Rose,
Whitehall I followed the lives
of 18,000 civil servants. Not
only did it provide valuable
information about the key
lifestyle factors associated
with cardiovascular and
respiratory disease, guiding
public health policy and
practice, it revealed a
remarkable socioeconomic
gradient in health: contrary
to expectations, stress and
heart disease afflicted those
at the bottom of the hierarchy
more than those at the top.
Moreover, the effect was
not just a difference between
those at the very top and
those at the bottom. It was
a genuine gradient, with men
at every level faring better
than those below them
and worse than those
above them.
The socioeconomic gradient
has become akin to a
fundamental, albeit unwritten
law of epidemiology. It has
been seen repeatedly,
in a multitude of situations,
across numerous countries,
affecting a vast range of
conditions.
Partly it arises because
lifestyle behaviours are
themselves socially
patterned – the less well-off
tend to have poorer diet,
smoke more and exercise
less. But these do not fully
account for the gradient.
Many other factors contribute
to the gradient, and these
POPULATION HEALTH UCL School of Life and Medical Sciences
21
Gut feelings
A throw of the dice
Why is there such a strong socioeconomic gradient
in bowel screening?
Principles established by Gregor Mendel are helping
researchers make sense of markers associated with disease.
Despite concerted efforts to make bowel cancer screening
available to all regardless of their circumstances, take-up shows
a marked socioeconomic gradient, with people from poorer areas
significantly less likely to participate. Part of the reason, suggests
a team led by Professor Jane Wardle and Dr Christian von
Wagner, lies in the way participants weigh up the short-term and
long-term implications of bowel screening.
The bowel cancer screening programme is open to everyone
aged 60–69. They are sent a do-it-yourself kit for collecting and
returning a stool sample. The test is free and sent directly to
recipients’ homes, so there are no obvious practical or economic
barriers to participation.
Yet Professor Wardle’s team discovered a marked gradient
in responses. In the most affluent areas, 61 per cent of people
responded; in the least affluent areas, just 35 per cent. Given the
significant benefits of participating – mortality can be reduced
by up to 27 per cent through regular screening – this disparity
is troubling.
The findings imply attitudinal differences to screening
– or disease prevention more generally – among different
socioeconomic groups. To explore this issue, the UCL team
examined attitudes to screening in people who had indicated they
might participate in a separate bowel screening trial (of flexible
sigmoidoscopy). Take up again showed a strong socioeconomic
bias – 63 per cent in the most affluent areas, 38 per cent in the
least affluent. The goal was to assess, in a quantifiable way, if any
attitudes correlated with socioeconomic status were associated
with the ultimate decision to attend screening.
In particular, the team examined a concept known as ‘future
orientation’ – broadly speaking, having relatively shorter-term or
longer-term perspectives. They found that a tendency to focus on
the short term – known to be associated with lower socioeconomic
status – was a significant factor influencing the decision to attend.
Those who did not attend tended to overweigh the short-term
obstacles and underappreciate the long-term benefits.
Although not the full story, the results begin to shed light on the
basis of an important health-related behaviour. In practical terms,
they also suggest ways in which the socioeconomic imbalance
could be addressed, for example by emphasising the short-term
benefits of participating in screening, such as peace of mind.
For complex diseases, it is useful to have simple biochemical
markers that faithfully track disease severity and progression.
They can be useful tools in diagnosis and risk prediction and,
potentially, valuable therapeutic leads. But markers are typically
identified by association, so must be viewed with caution: they may
be the result rather than the cause of disease, or a byproduct of
more fundamental disease processes. The distinction is extremely
important: there is no point developing therapies to lower levels of
a marker if it is not directly related to a disease. To tackle this issue,
Dr Aroon Hingorani is using a technique inspired by the ‘father of
genetics’, Gregor Mendel.
‘Mendelian randomisation’ is based on Mendel’s second law,
which states that units of heredity (genes as we now know them)
are distributed at random to gametes and hence to the next
population. Crucially, once the die has been cast, the distribution of
genes cannot change, so will not be affected by other risk factors
(as biochemical markers may be). Hence, if a marker is directly
contributing to a disease, then a gene raising levels of that marker
should put people at greater risk of disease.
Professor Hingorani and colleagues have used this approach
to examine the role of C-reactive protein (CRP) in coronary heart
disease. CRP is a circulating marker of inflammation and its levels
correlate with risk of heart disease. Since atherosclerosis has a
strong inflammatory element to it, it was a reasonable assumption
that CRP was contributing directly to atherosclerosis and heart
disease.
To test this idea, Professor Hingorani examined the association
between genetic variants in the CRP gene, circulating CRP levels
and measures of atherosclerosis or the incidence of heart disease
in different cohorts. Certain variants reliably increase CRP levels
so should put individuals carrying those variants at greater risk of
pathology or disease. In reality, they do not. Once the influence of
other risk factors is stripped away, having a CRP-raising allele has no
impact on heart disease risk. A very large international meta-analysis
has reinforced these findings.
Thus CRP is almost certainly not driving disease. More generally,
the results highlight the power of genetics and Mendelian
randomisation to delve deeper into the meaning of associations.
von Wagner C et al. Inequalities in participation in an organized national
colorectal cancer screening programme: results from the first 2.6 million
invitations in England. Int J Epidemiol. 2011;40(3):712–8.
Wensley F et al. Association between C reactive protein and coronary heart
disease: mendelian randomisation analysis based on individual participant
data. BMJ. 2011;342:d548. doi: 10.1136/bmj.d548.
Kivimäki M et al. Does high C-reactive protein concentration increase
atherosclerosis? The Whitehall II Study. PLoS One. 2008;3(8):e3013.
von Wagner C, Good A, Whitaker KL, Wardle J. Psychosocial
determinants of socioeconomic inequalities in cancer screening
participation: a conceptual framework. Epidemiol Rev. 2011;33(1):135–47.
Whitaker KL et al. Socioeconomic inequalities in colorectal cancer
screening uptake: does time perspective play a role? Health Psychol.
(in press).
22
POPULATION HEALTH UCL School of Life and Medical Sciences
...our health and well-being depends not just on
our genes, or what we eat, or what infections we
are exposed to, but also on what jobs our parents
did, their parenting style, what kind of education
we had, and how we are treated at work.
are often out of our control –
how we are treated at work,
for example, and how we
were brought up (as well as
our genetic inheritance).
There is also the fascinating
question of why certain
health behaviours are
socially patterned. Professor
Jane Wardle and colleagues,
for example, have examined
why there is a social
gradient in uptake of bowel
cancer screening, despite
exhaustive efforts to avoid
inequality in access (see
page 22). At least part of
the answer can be put down
to different psychological
attitudes to screening
in socioeconomically
disadvantaged groups.
Launched in 1985, Whitehall
II, the follow up to Whitehall
I, has confirmed the
socioeconomic gradient and
extended its predecessor’s
findings into other areas,
such as mental health and
well-being. It has begun
to explore some of the
biological mediators that
turn social phenomena into
physiological effects.
The British Regional Heart
Survey approached similar
questions to Whitehall I
from a different angle. It
was originally established
in the 1970s to investigate
regional differences in heart
disease, which at one point
were thought to be linked
to geographical variation in
hard water supply. The hard
water hypothesis did not hold
water – hard water was not
protective against hardened
arteries.
In fact, geographic
differences are largely
accounted for by regional
variation in conventional
risk factors: heart disease is
more common where people
smoke more, have a poor
diet and take less exercise.
The 1946 and 1958 birth
cohorts have also generated
a wealth of information on
lifestyle factors and adult life.
As birth cohorts, they have
been able to cast light on the
impact of early life events.
Data from the 1946 cohort,
for example, were among the
first to suggest that low birth
weight for gestational age
was a risk factor for later-life
metabolic conditions. This
fed into the influential ‘Barker
hypothesis’, which linked
poor maternal nutrition to
the ‘programming’ of fetal
metabolism, preparing
a newborn for a life of
hardship. Unfortunately,
this may leave them poorly
adapted to a life of plenty.
The multidisciplinary
nature of the birth cohorts
has provided unrivalled
opportunities to explore
links between health and
social, economic, domestic
and other circumstances.
Indeed they have done
much to emphasise the
interconnectedness of these
domains – our health and
well-being depends not just
on our genes, or what we
eat, or what infections we are
exposed to, but also on what
jobs our parents did, their
parenting style, what kind
of education we had, and
how we are treated at work.
Indeed, much of the recent
Marmot Review’s policy
framework for tackling health
inequalities is explicitly social
in nature (see page 30).
While cohorts have
traditionally focused
principally on environmental
influences on health, they are
increasingly being integrated
with genetic-based
approaches. Advances in
high-throughput genetic
analysis are offering a wealth
of opportunities to apply
genetic techniques at a
population-based level.
Most common diseases are
affected by genes, but not
in a simple deterministic
way. A great many genetic
variants influence common
diseases, but each is likely
to have only a small effect.
New genetic tools are
being used to identify these
variants in collections of
patients, but their impact can
also be explored in large,
well-phenotyped population
cohorts.
POPULATION HEALTH UCL School of Life and Medical Sciences
23
There is now a growing trend
to use population cohorts to
search for genetic variants
affecting disease-relevant
phenotypic and physiological
traits, taking advantage
of cohorts’ excellent
phenotypic data.
In addition, cohorts provide a
way to examine the impact of
disease-associated variants
in ‘normal’ populations.
One further advantage
is that cohorts can add a
life-course perspective,
shedding light on when a
genetic variant has its effect.
The emerging discipline of
‘genomic epidemiology’ is
thus likely to be of profound
importance. One other
application is ‘mendelian
randomisation’, which can
be used to test whether an
association – say between
a biomarker and a disease
– is really indicative of a
causal role in disease or
a byproduct of some more
fundamental link.
For individuals, the
implications are less clear.
Although genetic profiling
has the potential to be
used for risk prediction,
it is doubtful that it can
yet provide sufficiently
useful information to guide
healthcare or personal
health beyond traditional
24
guidance (eat more fruit,
don’t smoke). One potential
use may be to refine
treatments – being explored
in the FOCCS ovarian
cancer trial and for familial
hypercholesterolaemia
(see companion volume
on Translation and
Experimental Medicine).
More generally, large-scale
genetic studies identify leads
for follow up in laboratory
studies, shedding light on
mechanisms of disease.
Professor Andrew Phillips
and colleagues have
been working with some
of the world’s largest and
longest-running cohorts of
people with HIV. As well
as generating important
findings on treatment,
monitoring of these cohorts
has revealed the emergence
of resistance to antiretroviral
drugs. This information
again feeds into laboratory
studies, with investigations
by Professor Deenan
Pillay and colleagues of the
molecular mechanisms of
drug resistance.
Population data can
also be used to support
mathematical modelling of
transmission. Such studies
can be used to explore
the potential of variation
in therapy, in ‘virtual trials’
Flu Watch has targeted several thousand
households directly, collecting nasal swabs from
participants to ensure accurate diagnosis.
that would be impossible to
conduct in real-life situations.
Flu is an ongoing public
health concern, exacerbated
by the recent H1N1 swine flu
pandemic. Understanding
the transmission of flu is
challenging: the flu strains
in circulation change every
year, and reporting through
general practice may give
an incomplete picture of flu
in the community, as only a
proportion of people seek
treatment. In response to the
threat from H1N1 swine flu,
Dr Andrew Hayward was
funded by the MRC and the
Wellcome Trust to extend the
‘Flu Watch’ project, a unique
nationwide collaboration
characterising flu strains
circulating in the community.
Flu Watch has targeted
several thousand households
directly, collecting nasal
swabs from participants to
ensure accurate diagnosis.
The study revealed a
high incidence of mild
or asymptomatic H1N1
infections. Strikingly,
even though visits to
GPs surged during the
summer pandemic, the
POPULATION HEALTH UCL School of Life and Medical Sciences
Flu Watch data showed
no corresponding jump
in infections – the effect
probably reflected a change
in people’s health-seeking
behaviours in the face of
intense media coverage.
The study has tracked
the changing nature of
circulating flu strains, with
pandemic H1N1 having
largely ousted seasonal
H1N1 and a previously
dominant H3N2 strain.
The results have provided
a much clearer picture
of the reality of the H1N1
pandemic and seasonal
flu. Flu Watch results are
also shedding light on the
impact of disease-control
initiatives, and of antiviral
drug and vaccine use, while
analysis of blood samples
should reveal which aspects
of the immune response are
associated with protective
immunity. The results will
help to shape the response
to future flu epidemics, and
are also helping researchers
more accurately model
flu outbreaks and plan
interventions.
Heart breaking
The magic number
Influenza infections may be responsible for large
numbers of heart attacks.
When is the right time to begin antiretroviral therapies?
Despite accumulating evidence that influenza virus can affect
the heart and circulatory system, there has been no definitive
demonstration that influenza infections are a cause of clinical
heart problems. A systematic review carried out by UCL MRC
clinical fellow Dr Charlotte Warren-Gash, Dr Andrew Hayward
and Professor Liam Smeeth of the London School of Hygiene
and Tropical Medicine has clearly shown a connection between
the virus and the incidence of heart attacks, and some evidence
that vaccination might be protective.
The group looked at 42 publications describing 39 studies,
the earliest dating back to 1932. All reports at a population level
found an increase in the numbers of deaths due to heart disease
or numbers of heart attacks when influenza virus was circulating.
Moreover, the virus appears to have a significant effect – 35–50
per cent of excess deaths due to influenza could be attributed
to cardiovascular causes.
A range of observational studies in different settings likewise
reported links between acute respiratory infections – influenza
in particular – and heart attacks, and a less strong link to deaths
associated with cardiovascular conditions.
The picture was more mixed for vaccination. Four out of
eight observational studies found vaccination to be beneficial.
Of two small randomised controlled trials, one found evidence
for significant benefits while the other was inconclusive. Larger
studies would be needed to provide a conclusive answer, but the
evidence collectively suggest that improving vaccine coverage
in at-risk populations – in 2008/09 vaccine coverage in chronic
disease groups was less than 50 per cent – would help to reduce
the number of cardiovascular events triggered by influenza
infections.
Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute
myocardial infarction or death from cardiovascular disease: a systematic
review. Lancet Infect Dis. 2009;9(10):601-10.
The development of antiretroviral drugs raised hopes that HIV could
be eliminated from patients. Such hopes were dashed when it was
discovered that HIV could persist at low levels in reservoirs in the
body. Patients will therefore have to take antiretrovirals for long
periods, probably the rest of their lives. To protect them from the
short-term and long-term adverse effects of antiretroviral drugs,
treatment has typically been initiated only when levels of the immune
cells infected by HIV – CD4 cells – fall below a particular threshold.
The work of Professor Andrew Phillips and colleagues has done
much to influence what this threshold should be.
Professor Phillips has worked with some of the world’s longest
running cohorts of people living with HIV, recruited from HIV clinics
around the UK in the 1980s. Antiretroviral drugs were a life-saver for
these individuals, but had serious side-effects. Combined with fears
about the development of resistance, this led to the belief that they
should be used sparingly. If patients still had reasonable CD4 cell
numbers, it was argued, the benefits of giving them such powerful
drugs might not outweigh the risks.
In one early strategy, treatment was initiated at a CD4 count of
250 CD4 cells per cubic millilitre but halted when numbers rose
above 350. However, the international SMART (Strategies for the
Management of Antiretroviral Therapy) study found that such
‘episodic’ treatment increase the risk not only of AIDS disease
but also of several non-AIDS diseases and of death.
Although drug use still has to be weighed against side-effects,
the development of improved drugs tilted the balance firmly towards
earlier treatment, and 350 is now the widely used threshold. However,
it is still empirically defined – no clinical trial has ever directly tested
its validity. Indeed, untreated HIV-infected individuals with sturdy
CD4 cell counts had a modest but significantly higher death rate than
the general population, and lower CD4 levels were associated with
higher mortality even above the 350 threshold.
As the longevity of successfully treated people with HIV now
approaches that of the general population (at least in the developed
world), such discrepancies are troubling. Hence the magic number
of 350 may yet be revised upwards. Indeed, with collaborators in
Denmark, Professor Phillips is involved in a trial of HIV patients with
CD4 counts above 500, comparing immediate start with initiation at
350. This should reveal whether early therapy is beneficial to patients,
and it may also have population benefits by reducing transmission.
El-Sadr WM et al. CD4+ count-guided interruption of antiretroviral treatment.
New Engl J Med. 2006;355(22):2283–96.
Sterne JA et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet.
2009; 373(9672):1352–63.
Lodwick RK et al. Death rates in HIV-positive antiretroviral-naive patients with
CD4 count greater than 350 cells per microL in Europe and North America: a
pooled cohort observational study. Lancet. 2010;376(9738):340–5.
POPULATION HEALTH UCL School of Life and Medical Sciences
25
A long legacy
QuIRC of fate
The roots of adult obesity may lie in early life experience –
and even in the womb.
A newly developed toolkit provides an internationally
validated tool for assessing facilities for people with
long-term mental health problems.
Adult obesity is a risk factor for many conditions and a growing public
health concern. Adult behaviours are seen as central to obesity, and
are the target of numerous interventions, yet early-life factors are also
an important influence on adult weight. Working with the 1958 British
Birth Cohort, Professor Chris Power and colleagues documented
early signs of the ‘obesity epidemic’ and have identified some of
the early-life factors contributing to it.
A comparison between the 1958 and 1946 cohorts provided
graphic evidence of the roots of the epidemic. Despite being born
just 12 years later, the 1958 cohort grew more rapidly and ended up
taller. Although no bigger at birth, they were on average 1 cm taller in
childhood, grew more rapidly, ending up 3–4 cm taller in adolescence.
BMI trajectories diverged markedly from early adulthood – by midadulthood the 1958 cohort had 6–7 cm larger waists and double
the levels of obesity.
Greater prosperity and the ready availability of food were clearly
important factors in these changes. But work on the 1958 cohort
points to much earlier influences on adult obesity.
One striking observation has been the link between early-life
adversity and adult obesity. Even mild forms of adversity – strict
upbringing, physical punishment, verbal abuse, lack of parental
interest – were significant risk factors for poor glucose control
in adulthood (a proxy for diabetes risk). This increased risk was
mediated entirely through adult obesity. Several adversities increased
the risk of obesity by 20–50 per cent.
Obesity risk can be increased by even earlier events. Maternal
smoking substantially increased the risk of mid-life obesity, equating
to an average increase in waist size of 2 cm.
Studies of the 1958 cohort were among the first to show that low
birthweight, linked to maternal smoking or other factors, increased the
risk of adult health problems such as type 2 diabetes. Interestingly,
work on the 1958 cohort suggests that this effect is mediated through
an association with adult obesity – risks are not increased for lowbirthweight individuals who are not overweight as adults.
Recently, the 1958 cohort has begun contributing to genetic
research. Thanks to its large size and excellent phenotypic data,
the cohort was used as a control group by the Wellcome Trust Case
Control Consortium and is now involved with international consortia
studying genetic influences on physiological variables.
Li L, Hardy R, Kuh D, Lo Conte R, Power C. Child-to-adult BMI and height
trajectories: a comparison of two British birth cohorts. Am J Epidemiol.
2008;168:1008–15.
Despite widespread moves towards ‘deinstitutionalisation’, or
care within the community, people with severe mental health
problems are often treated in long-term facilities. To help improve
standards, the ten-country, EC-funded ‘DEMoBinc’ project, led by
Dr Helen Killaspy, has developed an internationally validated tool
for assessing the quality of these institutions.
People with long-term mental health problems are among the
most socially excluded. Their conditions are associated with
impairments of thinking and motivation that disrupt their ability
to function. They may also have other problems that slow their
recovery, such as substance misuse and challenging behaviours.
For many years, the answer was simply to confine them to
asylums. Deinstitutionalisation is gradually being introduced.
However, even in deinstitutionalised countries, longer-term
facilities are still used for the most difficult-to-treat patients, and
across Europe, most people with severe problems are treated in
institutions. Although many offer high standards of care, there is
undoubtedly often room for improvement.
To develop a framework for assessing quality of care, the
project undertook a systematic literature review, consulted
with international experts, and reviewed care standards in ten
European countries. A draft toolkit was rigorously piloted in over
200 units across the ten countries and tested for reliability, which
confirmed that the toolkit was robust, practical to use and wellreceived by facility managers. Toolkit ratings were also validated
against patients’ experiences of care. The final version comprises
145 questions assessing seven domains of care.
A web-based version of QuIRC is available in ten languages
at www.quirc.eu. It has already been incorporated into the UK’s
peer-accreditation process for mental health rehabilitation units
(coordinated by the Royal College of Psychiatrists’ Centre for
Quality Improvement), and Dr Killaspy is leading a five-year
NIHR-funded programme (‘REAL’, Rehabilitation Effectiveness for
Activities for Life) which is collating comprehensive national data
on units in England. A similar exercise is underway in Portugal,
and there are plans for national projects in many other countries.
QuIRC is an accessible and useful tool that can be used for
quality assessment and benchmarking for long-term mental
health facilities across Europe. Given the potential vulnerability of
those that use these facilities, it is a much-needed resource that
provides a powerful lever to drive up standards of care.
Thomas C, Hyppönen E, Power C. Obesity and type 2 diabetes risk in mid
adult life: The role of childhood adversity. Pediatrics. 2008;121:e1240–9.
Killaspy H et al. The development of the Quality Indicator for Rehabilitative
Care (QuIRC): a measure of best practice for facilities for people with
longer term mental health problems. BMC Psychiatr. 2011;11:35.
Thomas C, Hyppönen E, Power C. Prenatal exposures and glucose
metabolism in adulthood: are effects mediated through birthweight and
adiposity? Diabetes Care. 2007;30:918–24.
Turton P et al. Promoting recovery in long-term institutional mental health
care: an international Delphi study. Psychiatr Serv. 2010;61(3):293–9.
Power C, Atherton K, Thomas C. Maternal smoking in pregnancy, adult
adiposity and other risk factors for cardiovascular disease. Atherosclerosis.
2010;211:643–8.
26
POPULATION HEALTH UCL School of Life and Medical Sciences
Taylor TL et al. A systematic review of the international published literature
relating to quality of institutional care for people with longer term mental
health problems. BMC Psychiatr. 2009;9:55.
Health service research
While cohorts provide a
strong public health focus,
UCL also has extensive
programmes in health
services and implementation
research. These encompass
both clinical trials, primarily
focused on primary care
interventions, and studies
of healthcare delivery within
the NHS. Much of this work
draws on close links with
associated NHS bodies,
particularly ‘UCL Partners’
(see page 3).
Research has a strong
focus on mental health and
treatment in general practice.
Development of evidencebased tools for prediction
of depression and anxiety
has been one important
element. The Priment
Clinical Trials Unit is hosting
several studies examining
depression or other mental
health issues, particularly
schizophrenia. Trials are
examining management
of chronic depression
by practice nurses
(PROCEED), prevention
of depression in primary
care (PREDICTPREV), and
rehabilitation for people
Health data analysis
with chronic mental health
conditions (REAL).
Professor Rosalind Raine,
Director of the Centre for
Applied Health Research,
leads a programme
of studies providing
information directly relevant
to healthcare delivery. This
work is particularly focused
on healthcare inequalities,
in a range of healthcare
settings and for a wide range
of conditions (see page
34), and health economics,
drawing on the expertise of
Steve Morris, Professor of
Health Economics.
Current areas of interest
include the relationship
between use of healthcare
and health inequalities (a
five-year programme funded
by the Department of Health)
and clinical decision-making
by groups of clinicians
(including NICE Guideline
Development Groups) and its
impact on social inequalities.
Evaluations are also
undertaken of public health
and healthcare interventions,
including the Department of
Health Heatwave Plan and
community mental health
interventions.
A further important theme
– and one of particular
importance in the UK – has
been the analysis of routinely
collected health data. As
well as providing a source
of data on how healthcare is
actually delivered to patients,
such studies are invaluable
for retrospectively analysing
potential influences on health
or outcomes. They also
provide a mechanism for
studying rare events where
it would be impractical to
organise large trials.
A number of studies have
analysed data held in
the Health Information
Network database and the
General Practice Research
Database. Findings have
illuminated a number of
areas, from risk of suicide
and cardiovascular death
in severe mental illness
to patterns of antibiotic
prescribing.
A further important source of
information can be routinely
collected population data,
such as the UK’s Adult
Psychiatric Morbidity Survey.
Analyses have revealed
worryingly high levels of
suicidal thinking (one in six
of the population had had
death wishes or considered
suicide) 10 and of mental
distress in non-heterosexual
populations (roughly
double levels seen in the
heterosexual population) 11,
and illustrated the long-term
adverse impact of sexual
abuse12. More positively,
studies have also revealed
that the UK population is,
for the most part, in a good
mood – 40 per cent very
happy and 52 per cent fairly
happy13.
10 Bebbington PE et al. Suicidal ideation, self-harm and attempted suicide:
results from the British psychiatric
morbidity survey 2000. Eur Psychiatry.
2010;25(7):427–31.
11 Chakraborty A, McManus S,
Brugha TS, Bebbington P, King M.
Mental health of the non-heterosexual
population of England. Br J Psychiatry.
2011;198(2):143–8.
12 Bebbington P et al. Childhood
sexual abuse and psychosis: data from
a cross-sectional national psychiatric
survey in England. Br J Psychiatry.
2011;199:29–37.
13 Cooper C et al. Happiness across age
groups: results from the 2007 National
Psychiatric Morbidity Survey. Int J
Geriatr Psychiatry. 2011;26(6):608–14.
POPULATION HEALTH UCL School of Life and Medical Sciences
27
The benefits of bilirubin
Can the web cut problem drinking?
Bilirubin, a blood breakdown product, might be
protective against a range of respiratory conditions.
A ‘psychologically enhanced’ online intervention reduced problem
drinking – but so did its comparator.
Routinely collected data held in health records are a
valuable repository of information for exploring the origins
of ill-health, or factors that might be protective. With
evidence emerging that bilirubin might have beneficial
health effects, Dr Laura Horsfall and colleagues examined
the health records of more than half a million patients to
look for associations between blood bilirubin levels and a
range of respiratory ailments. Their analysis revealed that
relatively high levels of bilirubin, within the normal range,
were associated with less respiratory illness.
The study looked at data on 504,206 adults without
bilirubin-linked disease whose health records were part of
the General Practice Research Database. Blood bilirubin
levels were compared with the incidence of lung cancer,
chronic obstructive pulmonary disease (COPD) and
all-cause death.
In all three cases, relatively high levels of blood bilirubin
(though still within the range considered normal) were
associated with health benefits. Each 0.1 mg/dl increase
in bilirubin levels was associated with an 8 per cent
decrease in the incidence of lung cancer for men and
an 11 per cent decrease for women, and a 6 per cent
decrease in COPD and a 3 per cent decrease mortality
for men and women.
A study such as this cannot identify the mechanisms
by which bilirubin has a protective effect, though there is
some evidence that it has anti-oxidant properties and may
be protecting cells from damaging oxidant molecules.
In the long term, suppressing the activity of the liver
enzyme that eliminates bilirubin could be a considered
as a therapeutic strategy to protect against respiratory
disease.
The study also highlights the advantage of research
based on large numbers of health records. The UK is one
of the few countries where this kind of study could have
been carried out.
Regular excessive drinking is extremely common and has considerable
health and social impact. So the demonstration by Dr Elizabeth Murray
and colleagues that an innovative web-based intervention, Down Your Drink,
halved alcohol consumption might be considered good news. However, its
comparator – a simple text-based website – was equally effective, leaving
open the question of what is actually responsible for the drop in alcohol
consumption.
The Down Your Drink website was the brainchild of Dr Stuart Linke, an
Islington-based clinician. Swamped with people seeking help for problem
drinking, he developed a web-based resource that he could direct patients
to, with support from the charity Alcohol Concern. An initial analysis found
that users of the site cut their alcohol intake, but in the absence of a control
group it was impossible to conclude that this was due to their use of the site.
Despite no further promotion or development, the site continued to attract
a steady stream of traffic, encouraging Dr Linke and Dr Murray to develop
an enhanced version. The new site was founded on validated psychologically
based approaches to alcohol reduction and was redesigned following
extensive dialogue with users.
To evaluate the new resource, the team used a simple text-based website
as comparator. The site was again accessible via the Alcohol Concern
website, with users randomly directed to one or other resource.
The trial recruited nearly 8000 participants. Down Your Drink again
achieved very positive results, reducing alcohol consumption by about a half.
Strikingly, though, people using the simple website cut their drinking by a
similar amount.
The findings are thus difficult to interpret. Participants using the control
site may have sought additional material elsewhere, helping them to achieve
better results. It is also possible that the assessments used in the trial
prompted all participants to cut down intake.
In the meantime, some health authorities have been impressed enough
to implement a version of the resource. However, implementation is raising
a further issue, as it is proving difficult to persuade healthcare workers
to refer individuals – partly because the numbers identified as having
problematic drinking habits are staggeringly high; the perception is that
something so common cannot be a problem. The fact that deaths from liver
cirrhosis have increased tenfold in some age groups over the past 30 years
suggests that it is.
Horsfall LJ et al. Serum bilirubin and risk of respiratory disease
and death. JAMA. 2011;305(7):691–7.
Wallace P et al. On-line randomized controlled trial of an internet based psychologically
enhanced intervention for people with hazardous alcohol consumption. PLoS One.
2011;6(3):e14740.
Linke S, McCambridge J, Khadjesari Z, Wallace P, Murray E. Development of a
psychologically enhanced interactive online intervention for hazardous drinking.
Alcohol Alcohol. 2008;43(6):669–74.
28
POPULATION HEALTH UCL School of Life and Medical Sciences
New technology also holds promise as a way
of engaging members of the public in their own
healthcare. Despite much enthusiasm, however,
the area remains one of great potential rather
than concrete progress.
Specialist expertise in
electronic health records
is held in the UCL Centre
for Health Informatics and
Multiprofessional Education
(CHIME). CHIME has played
an important role in UK and
European collaborations
establishing data standards
for clinical information and
ensuring data privacy. In
practical terms, its work with
the community cardiology
services of the Whittington
Hospital NHS Trust has led
to web-based applications
supporting a range of clinical
functions at the Whittington
and at neighbouring hospital,
primary care and pharmacy
sites. CHIME is also
engaged in research into
computer tools to support
clinical decision making,
for example through the
development of computerassisted diagnosis tools and
analysis of the processes
by which clinical guidelines
are developed.
New technology also
holds promise as a way
of engaging members
of the public in their own
healthcare. Despite much
enthusiasm, however, the
area remains one of great
potential rather than concrete
progress. UCL’s e-Health
Unit, led by Dr Elizabeth
Murray, is engaged in a
range of projects covering
sexual health promotion
(‘Sexunzipped’), selfmanagement for type 2
diabetes and alcohol use
(‘Down your Drink’), and is
also exploring the impact
of new technologies and
information gathering on
doctor–patient relationships.
Part of the enthusiasm for
online projects reflects
their potential to provide
an in-depth, individualised
experience on a very
large scale, with very
low incremental costs.
In one area, alcohol use,
a systematic review by
Dr Murray and colleagues
suggests online interventions
can work, and the Down
Your Drink site has gathered
encouraging data (see page
28). Success is more likely if
interventions are rooted in a
strong theoretical framework,
to ensure that evidencebased approaches are
adopted and that learning
can be applied to future
developments. It is also
vital to get users involved
in development from the
very beginning.
The field is new and rapidly
evolving, and exactly how
online approaches (or
other new technologies)
will ultimately affect formal
healthcare or public health
is hard to predict. The type
2 diabetes project aims
to integrate web-based
approaches into clinical care,
while other interventions may
be better targeted directly at
the public. By reaching large
numbers of people, even
a small change could have
substantial benefits at a
population level, at very
low cost.
Predicting depression
A simple screening tool might be sufficient to identify
patients at risk of depression.
Major depression is common and disabling. As with many
conditions, prevention is better than cure. But while well-validated
tools have been developed for common conditions such as
cardiovascular disease, GPs have had no equivalent ways to
identify reliably those at risk of depression. To remedy this situation,
Professor Michael King and colleagues have developed and
tested a simple screening tool for assessing risk of depression,
PredictD, and adapted the tool for use with anxiety disorders.
A healthcare screening tool needs to be sensitive, specific and
practicable for everyday use. Many factors are known to increase
the risk of depression but individually are of little value in guiding
clinical decision-making.
To develop a practical healthcare tool, Professor King and
colleagues gathered data on 39 known risk factors for depression
in more than 5000 non-depressed attendees at general practices
in six European countries. By identifying those who experienced
depression at six months or 12 months, the team was able to
develop a highly specific and sensitive risk algorithm. Furthermore,
the algorithm performed well when tested with an entirely
independent sample of patients in Chile.
The algorithm contains just nine factors, four of which are
potentially open to change (physical health score, current mental
health score, unsupported difficulties at work and experience
of discrimination). And although the remaining five risk factors
(age, sex, educational level, past experience and family history of
depression) cannot be changed directly, they help to identify highrisk people who can be supported through active listening or given
advice about lifestyle.
Although more work needs to be done to assess its practical
utility, PredictD has the potential to be used as a simple screening
tool in general practice to identify patients at risk of depression.
Moreover, its international development suggests it could have
widespread applicability.
The work has also led to a follow-up project to develop a similar
tool for generalised anxiety and panic syndromes, using a similar
methodology and starting with 38 known risk factors. In fact, the
anxiety algorithm, PredictA, shares several constituents with
PredictD, suggesting the two conditions may share at least some
underlying mechanisms.
King M et al. An international risk prediction algorithm for the onset of
generalized anxiety and panic syndromes in general practice attendees:
predictA. Psychol Med. 2011; 41(8):1625–39.
King M et al. Development and validation of an international risk prediction
algorithm for episodes of major depression in general practice attendees:
the PredictD study. Arch Gen Psychiatr. 2008;65(12):1368-76.
POPULATION HEALTH UCL School of Life and Medical Sciences
29
The original ‘Whitehall’ cohort study overturned the
conventional view of work, stress and health – it was the
lower orders who suffered most, not the ‘stressed executive’.
Its follow-up, Whitehall II, is shedding more light on the links
between socioeconomic status and health.
The heart of
the civil service
While studying for a
PhD at the University of
California Berkeley in the
1970s, Michael Marmot
examined the incidence of
heart disease in Japanese
men who had migrated
to Hawaii and California.
He discovered that the
health advantage enjoyed
by Japanese men was
dissipated by migration –
and the greater their cultural
assimilation, the more their
health was affected.
The results graphically
illustrated the influence
of environment on heart
disease. But they also raised
interesting questions about
how living circumstances
could affect people’s health.
Returning to the UK,
Professor Marmot became
involved in the ‘Whitehall’
study – a pioneering
study examining the roots
of chronic conditions in
a cohort of 18,000 civil
servants. He was keen to
examine the influence of
social and cultural factors,
but the only even vaguely
relevant indicator was
employment grade (the UK
civil service being highly
hierarchical).
Remarkably, analysis of
heart disease data by
grade revealed a very clear
gradient: the further down
the employment ladder
30
someone sat, the worse
their health was likely to
be. This flatly contradicted
received wisdom. The most
senior mandarins, with the
supposedly most stressful
jobs, should have been the
ones most prone to heart
disease. Not only was the
reverse true – it was those
at the base of the pyramid
that fared worse – but there
was also a clear gradient of
effect: ill-health increased
at every step from top
to bottom.
So was stress not significant
after all? No: stress does
not come with power, but
with lack of power. The most
stressful circumstances
are experienced by those
further down the hierarchy,
who have increasingly
less control over their lives
and fewer opportunities
to influence what goes on
around them.
The marked socioeconomic
gradient apparent in the
Whitehall study has since
been seen in multiple
cohorts all over the world.
Almost anywhere anyone has
looked, the lower someone’s
socioeconomic status, the
worse their health is likely to
be. The first Whitehall study
is thus a landmark in one of
the most important health,
social and political issues of
the day – health inequalities.
In the UK, health inequalities
are dramatic. Life expectancy
differs by seven years
between rich and poor
neighbourhoods (disabilityfree life expectancy differs
by an astounding 17 years).
On essentially every measure
of health and well-being, a
gradient exists between rich
and poor (see Box).
Professor Marmot has been
instrumental in establishing
other important cohorts,
including the English
Longitudinal Study of
Ageing (see page 34) and
population cohorts in four
East European countries.
He also leads a Whitehall
follow up, Whitehall II.
Launched in 1985, Whitehall
II is tracking 10,000 civil
POPULATION HEALTH UCL School of Life and Medical Sciences
servants (this time including
women). As well as covering
some of the same territory
as Whitehall I, it is also
examining a wider range
of psychological and
psychosocial factors, diet
and links between social
circumstances, behaviour,
biology and disease.
Whitehall I (and many other
studies) revealed that
much of the socioeconomic
gradient could be linked
to socially patterned
health behaviours – such
as smoking or exercising
too little. One challenge is
to understand why these
behaviours show social
patterning (and ideally to
do something about them).
On the other hand,
Whitehall data also imply
that health behaviours
cannot fully account for the
socioeconomic gradient,
suggesting an important role
for other factors (particularly
other ‘life-course influences’,
such as neonatal and
childhood experiences and
even prenatal exposures).
A fuller understanding of
all these influences can
suggest when and how to
tackle health inequalities.
Perhaps most significantly,
they suggest that inequalities
need to be tackled at an
early age.
At a time when medical
science is increasingly
searching at the smallest
possible level for the causes
of disease, the Whitehall
studies are a reminder that
‘people interactions’, as well
as molecular interactions, are
fundamental to healthy lives.
“In this study of civil servants, a man’s grade
of employment was a stronger predictor of
his subsequent risk of CHD death than any
of the other major coronary risk factors.”
An ideologue with evidence
Professor Sir Michael Marmot has spent decades
collecting information on the detrimental impact of
inequalities on health, and trying to persuade those in
power to tackle them.
One of Michael Marmot’s first roles at the Whitehall study was
as a delivery boy. With an MD and freshly minted Berkeley PhD
to his name, his task was to deliver a copy of the first Whitehall
paper to the Lancet. The paper described the now classic risk
factors such as smoking and lack of exercise associated with
chronic diseases in British civil servants.
Professor Marmot’s discovery of the socioeconomic gradient
in these effects had a profound impact. The pervasiveness and
scale of the gradient has been demonstrated repeatedly. Rather
than just documenting health inequalities, though, he has been
actively involved in trying to eradicate them – the difficult territory
where science meets politics.
In the late 1970s, Sir Douglas Black produced the first national
report on health inequalities. Commissioned by a Labour
Government, by the time it was published a new Conservative
government had come to power and promptly suppressed it.
The issue was revisited in the 1990s by the Chief Medical
Officer of the time, Sir Donald Acheson, who invited Professor
Marmot to contribute. This led to a commission from the World
Health Organization to investigate the social determinants of
health. The resulting report, Closing the Gap in a Generation,
led the recent Labour government to ask Professor Marmot to
develop recommendations for tackling health inequalities in the
UK. Despite a change of government, Fair Society, Healthy Lives
(‘the Marmot Review’), published in 2010, has not suffered the
ignominious fate of the Black Report.
The Marmot Review collates a wealth of information on health
inequalities, and makes no bones about the need to tackle social
inequality in order to achieve health benefits. It is, he argues,
simply a matter of social justice. This position has not escaped
comment – one critic described Closing the Gap as ‘ideology
with evidence’. It is a criticism he is happy to embrace.
The WHO continues to pursue the social determinants agenda,
with a world conference hosted by the government of Brazil
taking place in October 2011. In Europe, work is underway on
a Regional European Health Policy that will examine social
determinants of health. Professor Marmot continues to press
home the key messages of the Marmot Review – that the
health gradient affects people significantly at all levels, at
enormous social and individual cost, and the policy tools exist
to do something about it. Academic outputs also continue
to accumulate, delivered these days by email rather than
overqualified messenger boy.
Marmot M et al. Employment grade and coronary
heart disease in British Civil Servants.
J Epidemiol Community Health 1978;32:244–9.
POPULATION HEALTH UCL School of Life and Medical Sciences
31
SECTION 4
How to age successfully
The key to a healthy old age is to live healthier in early life and to
adopt a positive frame of mind to ageing. It also helps to be wealthy…
32
POPULATION HEALTH UCL School of Life and Medical Sciences
With longevity continuing
to increase at a remarkable
rate – currently around
three months for every year
lived – health and well-being
in old age become ever
more important. Globally,
there were around 600
million people aged 60plus in 2000 and numbers
are projected to rise to 1.2
billion by 2025 and 2 billion
by 2050. Ageing is also of
profound importance to
healthcare systems: more
than half of an individual’s
lifetime healthcare costs
typically accumulate after
the age of 65.
A longer-living population
can be considered a great
achievement. However,
adding extra years to
lifespan is only one part of
the equation – quality of
life in those years needs
to be considered too. The
concept of ‘successful
ageing’ has become
increasingly popular.
Although not rigorously
defined, the term captures
a sense of later life free
from chronic diseases and
with the freedom to function
effectively, both physically
and mentally. The term
has been attributed to US
academic R J Havighurst in
the 1960s, who likened it to
‘adding life to years’ rather
than just ‘years to life’.
The concept of ‘successful ageing’ has become
popular. Although not rigorously defined, the term
captures a sense of later life free from chronic
diseases and with the freedom to function
effectively, both physically and mentally.
‘Ageing’ is in some senses
a counter-intuitive idea as
it does not equate simply
with number of years lived.
Differences in lifestyle
can mean that two people
who have lived the same
number of years are at quite
different stages of ageing.
Similarly, biological markers
of ageing – accumulated
damage to cells – do not
correspond directly to
years lived. Hence, just as
some 80-year-olds seem as
sprightly as 60-year-olds,
biological markers of ageing
may be equally divergent
from chronological age.
Ageing is accompanied
by a characteristic set
of changes, affecting
both physical and mental
function. Older people
typically experience a
decline in physical strength
and loss of muscle mass
as well as some loss of
cognitive powers. Many
conditions also show
an association with
age, including cancers,
chronic conditions and,
notably, dementia and
neurodegenerative
disorders.
Longitudinal studies
have enormous power
to shed light on ageing
at a population level.
In particular, they can
provide a life-course
perspective that examines
the consequences of past
life experiences on the
timing and nature of ageing.
Indeed, the take-home
message could be that
successful ageing begins at
birth – or even before.
One crucial factor is,
inevitably, socioeconomic
status. Findings from the
Whitehall II study (see
page 30) indicate that the
impact of socioeconomic
status actually increases in
old age14. Physical health
worsened more rapidly for
workers on lower grades,
such that the average
physical age of a 70-yearold in a high grade was
equivalent to that of a
62-year-old in a low grade.
Although mental health
improved at both ends of
the socioeconomic gradient,
those at the top gained
more, again increasing
health inequalities. Since
most of the civil servants
had retired at the time of
analysis, the results suggest
that occupational status
has long-lasting impacts,
and raise concerns about
a possible growth in
inequalities in old age.
14 Chandola T, Ferrie J, Sacker A,
Marmot M. Social inequalities in self
reported health in early old age: followup of prospective cohort study. BMJ.
2007;334(7601):990.
POPULATION HEALTH UCL School of Life and Medical Sciences
33
An ageing raw deal?
Much ado about ageing
Older patients may be being treated less favourably,
according to a large-scale analysis of GPs’ behaviour.
A comparison between ageing in the UK and the USA
ignited a firestorm of controversy in the USA, while
scarcely raising a ripple in the UK.
Since 2010 it has been against the law in the UK to discriminate
against people on the basis of their age. Even so, the research
of Professor Rosalind Raine and colleagues suggests that older
people are not receiving the same level of care as younger citizens.
GPs hold positions of considerable influence within the UK
National Health Service, not least by deciding who should be
referred for specialist treatment. In theory factors such as age
(or sex or socioeconomic circumstances) should have little or no
influence on these decisions. Yet an analysis of GP consultations
on more than 125,000 patients – 5500 with post-menopausal
bleeding, 23,000 with hip pain and 100,000 with dyspepsia –
revealed significant age-related inequalities in referral across all
three conditions.
This study made use of the Health Improvement Network
database, as did a further study examining drug prescribing
behaviour for stroke patients. Despite explicit guidance, just 25.6
per cent of men and 20.8 per cent of women received lipid-lowering
drugs for secondary prevention – and there was a clear age
gradient in the numbers receiving drugs. The odds of 80–89-yearolds receiving drugs was almost half that of 50–59-year-olds. This
is particularly shocking as drug use halved mortality – mortality
after one year was 5.7 per cent in patients receiving drugs and
11.1 per cent in those not prescribed them.
Similar trends were seen in an analysis of hospital data, and
treatment for three common cancers (colorectal, breast and lung
cancer) in half a million patients. Despite a national plan to reduce
inequalities in cancer care, age-related inequalities existed for all
three cancer types. Older people were more likely to be admitted
as emergencies rather than as planned admissions, and less
likely to have their preferred treatments. Planned admissions are
generally associated with better outcomes, so the disparities could
underlie age-related differences in survival.
Equity of access is a fundamental principle of the NHS. Yet for
age – as well as sex and socioeconomic status – that principle may
not be being met in practice.
McBride D, Hardoon S, Walters K, Gilmour S, Raine R. Explaining
variation in referral from primary to secondary care: cohort study. BMJ.
2010;341:c6267.
Raine R et al. Social variations in access to hospital care for patients with
colorectal, breast, and lung cancer between 1999 and 2006: retrospective
analysis of hospital episode statistics. BMJ. 2010;340:b5479.
Despite having just 5 per cent of the world’s population,
the USA accounts for more than half of all money spent on
healthcare globally. So when a study published by Professor
Sir Michael Marmot and colleagues found that seniors in the
UK generally enjoyed better health than those in the USA,
the impact was profound.
The work compared participants aged 55–64 in the US Health
and Retirement Survey and UK English Longitudinal Study of Ageing.
One factor common to both countries was the socioeconomic
gradient – in both the USA and the UK, the lower someone’s
socioeconomic status, the worse their health was likely to be.
Adjusting for purchasing power, the USA was spending almost
twice as much on its healthcare as the UK. Yet on seven key
measures of health – diabetes, hypertension, heart disease,
myocardial infarction, stroke, lung disease and cancer – UK seniors
were doing better than their US peers. Moreover, the findings were
not due to national biases in reporting: several biological markers
of disease showed similar patterns.
The US and UK health systems are quite different, with the UK’s
NHS providing free healthcare at the point of delivery and the
US relying on health insurance. Yet access to healthcare was not
the cause of the disparity: the vast majority of the US cohort had
health insurance.
The story was front-page news in the USA, and Professor Marmot
was still fielding media calls weeks later. A New York Times editorial,
headlined ‘Our sick society’, noted that “…Americans are so much
sicker that the richest third of Americans is in worse health than
the poorest third of the English.” Oddly, the UK media showed little
interest – a classic example of bad news being a stronger story than
good news.
Stung by the findings, the US National Institute on Aging asked
the National Research Council to examine the USA’s relatively poor
standing in life expectancy. Other studies have followed up the
ELSA analysis, identifying a similar pattern across other age groups
– leading one commentator to note that, “exporting the poorest
English to America might improve the average health status of both
countries!”
Curiously, conventional risk factors account for only a proportion
of the US–UK differences. There may be a deeper structural
explanation: the social support systems characteristic of the UK may
be having a hidden benefit, lifting health levels across the board.
Banks J, Marmot M, Oldfield Z, Smith JP. Disease and disadvantage in the
United States and in England. J Am Med Assoc. 2006;295(17):2037–45.
34
POPULATION HEALTH UCL School of Life and Medical Sciences
Whitehall II has also
generated evidence on
earlier influences on ageing.
A recent analysis suggested
that a rather sobering 13 per
cent of men and 15 per cent
of women could be said to be
ageing successfully15. As well
as midlife socioeconomic
status, successful ageing
was also predicted by
‘healthy lifestyle’ factors – not
smoking, diet and exercise.
Notably, though, it was also
affected by education (for
men) and height (particularly
for women), which probably
reflects childhood factors
such as nutrition. Interesting
sex differences were seen,
with moderate alcohol
consumption being important
for women and work support
for men.
Other cohorts are also
generating important
information on ageing,
not least the English
Longitudinal Study of Ageing
(ELSA), led by Professor
Sir Michael Marmot and
Professor Andrew Steptoe
in collaboration with
researchers from the Institute
of Fiscal Studies and the
National Centre for Social
Research. Modelled on the
US Health and Retirement
Study, it is intended to
provide an integrated view
of the health, economic and
social aspects of ageing,
and to provide a source of
evidence to inform UK health
and social policy. It samples
around 7000 people over the
age of 50 every two years.
ELSA has also shown that
the socioeconomic gradient
is felt as keenly in later life as
at earlier stages. Between
the first two waves of the
survey, participants aged
50–59 from the poorest fifth
of the population were more
than 10 times more likely
to die than their peers from
the richest fifth16. For most
measures relevant to health
and quality of life, greater
wealth is associated with
higher scores.
ELSA is part of a wider
European programme,
SHARE, the Survey of Health,
Ageing and Retirement in
Europe. First begun in 11
countries, it now covers
45,000 individuals aged 50plus across 13 countries.
Important European data are
also being collected through
the HAPIEE (Health, Alcohol
and Psychosocial Factors
in East Europe) study,
organised by Professor
Marmot and Dr Martin
Bobak, which is following four
cohorts in Russia, Poland,
the Czech Republic and
Lithuania. The health of East
Europeans typically lagged
that of West Europeans in
the Communist era, but this
effect was exacerbated by
the fall of Communism. Life
expectancy plummeted:
between 1990 and 1994,
male life expectancy in
Russia fell by six years to
57. However, life expectancy
has varied in complex ways
across East Europe.
The HAPIEE study is
exploring the theory that
alcohol consumption, diet
and nutrition, and economic
circumstances have been
responsible for reducing
life expectancy. Although
recent evidence suggests
more positive trends, data
analysed to date suggest
that unhealthy lifestyles are
having a significant impact
on health17.
Although originally
established to examine
factors affecting childbirth,
the 1946 Birth Cohort,
now the responsibility of
Professor Diana Kuh at
the MRC Unit for Lifelong
Health and Ageing, has
refocused on health and
well-being at the end of
life. The world’s longestrunning birth cohort, it will
provide a unique glimpse of
life-course influences, from
cradle to grave, on an ageing
population. The 1946 Birth
Cohort is part of a suite of
cohorts examining ageing,
known as HALCyon (Healthy
Ageing Across the Life
Course), which collectively
cover some 30,000
participants.
As with the Whitehall cohorts,
the 1946 Birth Cohort has
documented a wide range
of influences across the life
course that influence later-life
health and well-being. For
example, several factors have
been found to affect physical
capability in later life, which is
in turn predictive of mortality.
Interestingly, perceptions
of when old age begins
may be a good indicator
of future longevity. In the
Whitehall II cohort, those
who thought old age began
at relatively early ages were
likely to die sooner than
those who thought it began
at later ages. Attitudes were
influenced by current health,
as well as by socioeconomic
status, the extent of social
networks and perceived life
control. Similarly, in ELSA
surveys, those who think of
themselves as younger than
their actual age have better
health than those who think
of themselves as older.
Health inequalities could be
exacerbated if older people
receive less favourable
treatment by the NHS.
Indeed, Professor Rosalind
Raine and colleagues have
found evidence that older
people do not always receive
the same levels of care as
younger people, in primary
and secondary care (see
page 34). In trials, Professor
Michael King and colleagues
have shown that cognitive
behavioural therapy is an
effective treatment for elderly
people with depression,
even though they are rarely
offered it18.
Interventions relevant to
older people are among the
studies being carried out
at the Priment Clinical Trials
Unit. These include ProAge65, which aims to boost
exercise in people aged 65
15 Britton A, Shipley M, Singh-Manoux
A, Marmot MG. Successful aging:
the contribution of early-life and
midlife risk factors. J Am Geriatr Soc.
2008;56(6):1098–105.
16 Banks J, Breeze E, Lessof C, Nazroo
J. eds. Retirement, health and relationships in the older population in England:
the English Longitudinal Study of Ageing
2004 (wave 2). 2006. London: Institute
for Fiscal Studies.
17 Boylan S et al. Dietary habits in three
Central and Eastern European countries:
the HAPIEE study. BMC Public Health.
2009;9:439.
18 Serfaty MA et al. Clinical effectiveness of individual cognitive behavioral
therapy for depressed older people in
primary care: a randomized controlled trial. Arch Gen Psychiatry. 2009
(12):1332–40.
POPULATION HEALTH UCL School of Life and Medical Sciences
35
and over, and randomised
trials of cognitive stimulation
for dementia and of support
for carers of people with
dementia (all funded through
the NIHR). A study funded by
the Food Standards Agency,
led by Dr Alan Dangour of the
London School of Hygiene
and Tropical Medicine, is
examining whether vitamin
B12 supplements improve
cognitive function in older
people. In addition, the
HOPE trial is evaluating a
home-based intervention
for frail older people.
UCL also contributes to
other important research
infrastructure. It acts as
the north London hub
of the Mental Health
Research Network and is
the coordinating centre for
the north London hub of
DeNDRoN (Dementias and
Neurodegenerative Diseases
Research Network).
Dementia
Perhaps the most profound
challenge to successful
ageing, for individuals,
families and health services,
will come from dementia.
There are currently around
600,000 people in the UK
with dementia, a number
likely to rise to 840,000 by
2026 and 1.2 million by 2050.
Globally it accounts for more
years lived with disability
than stroke, heart disease
and cancer combined, and
the annual healthcare cost to
36
the UK is projected to rise to
a staggering £50 billion by
mid-century.
UCL researchers are at the
forefront of dementia health
research. Professor Steve
Iliffe, the UK’s only Professor
of Primary Care for Older
People, has made numerous
contributions to healthcare
guidelines, and helped to
establish the UK Department
of Health’s National Dementia
Strategy in 2008 (see page
37). Dr Elizabeth Sampson
(supported by Marie Curie
Cancer Care) has raised
awareness of the need for
palliative care for people
with dementia, as well as
characterising numerous
issues with hospital care
of elderly patients with
dementia (see page 37).
As well as affecting patients,
dementia can have a
substantial impact on carers.
Professor Gill Livingston,
Dr Claudia Cooper and
colleagues have drawn
attention to the problems
they face before a diagnosis
is given, when few support
mechanisms are available.
She has also documented
concerning levels of abusive
behaviour by carers towards
patients, one-third of whom
reported ‘significant’ levels
of abuse19. Even more
worryingly, follow up a year
later found an increase
in abusive behaviour,
associated with symptoms
of anxiety and depression
in carers20. Conversely, more
than a third of carers had
experienced abuse from the
person with dementia they
were looking after 21.
Dementia is also an important
theme of UCL’s Deafness,
Cognition and Language
research centre, led by
Professor Bencie Woll. The
centre is leading a project,
funded by the Alzheimer’s
Society, which aims to
improve early diagnosis and
management of dementia
among Deaf people who use
British Sign Language.
Almost nothing is currently
known about how dementia
affects Deaf people, or
how it could be diagnosed.
Researchers are studying
normal ageing with the help
of several hundred Deaf
people who meet each year
for a holiday organised by
the English Deaf Darby and
Joan Club. The team is also
exploring the experiences of
Deaf people with dementia
and their carers, to identify
their priorities for care
and how to improve early
identification and support
services.
A significant programme
of work at UCL is exploring
ways to use brain imaging to
provide earlier detection of
neurodegenerative disorders
(see companion volume,
Neuroscience and Mental
Health).
POPULATION HEALTH UCL School of Life and Medical Sciences
Over the longer term, ways
to promote more successful
ageing may come from a
better understanding of the
basic biological processes
involved in ageing. UCL
hosts one of the world’s
leading research centres
in ageing, led by Professor
Dame Linda Partridge – who,
among many honours, was
awarded the title ‘Living
Legend’ by Help the Aged
in 2006. Working mainly with
model organisms, Professor
Partridge’s Institute of
Healthy Ageing is gathering
key insight into the genes
and physiological processes
that affect ageing, work that
may suggest strategies to
promote healthier ageing
in people (see companion
volume, on Basic Life
Sciences).
19 Cooper C et al. Abuse of people with
dementia by family carers: representative cross sectional survey. BMJ.
2009;338:b155.
20 Cooper C, Blanchard M, Selwood
A, Walker Z, Livingston G. Family carers’ distress and abusive behaviour:
longitudinal study. Br J Psychiatry.
2010;196(6):480–5.
21 Cooper C, Selwood A, Blanchard M,
Livingston G. Abusive behaviour experienced by family carers from people with
dementia: the CARD (caring for relatives
with dementia) study. J Neurol Neurosurg Psychiatry. 2010;81(6):592–6.
Dying with dementia
Diagnosing dementia
Acute hospital wards are not geared up for patients with
dementia, and patients would rather not be there either.
Can a GP education programme improve the early
diagnosis of dementia?
Dementia currently affects some 700,000 people in the UK and
numbers are projected to surpass 1 million before mid-century.
Increasingly, people at the end of their lives will be suffering from
dementia, with multiple medical and social care needs. Supported by
Marie Curie Cancer Care, Dr Elizabeth Sampson has highlighted the
major problems associated with hospital admission for this group of
patients, as well as possible solutions based on coordinated palliative
care pathways.
The study of more than 600 acute hospital admissions of patients
aged over 70 revealed not only a significant prevalence of dementia
– 42.4 per cent overall, rising to 75.0 per cent in those over 90 – but
also alarmingly high numbers of undiagnosed cases, half of the total.
Patients with dementia fared significantly worse than those without –
those with most severe cognitive impairment were three times more
likely to die during admission.
Patients with dementia were also much more likely to suffer a
healthcare-related ‘adverse event’, possibly because medical staff
were not aware of walking difficulties or other deficits (several patients
with short-term memory problems were instructed to use call bells).
The results suggest that admission to hospital is not prolonging life for
meaningful periods. Ironically, the evidence also suggests that most
patients would prefer to die at home.
Working with the London Borough of Haringey, and Barnet, Enfield
and Haringey Mental Health Trust, Dr Sampson’s team has also
undertaken a more detailed examination of the experience of individuals
and agencies involved in a small number of terminal cases. This work
identified examples of good practice, as well as highlighting problem
areas and reasons why patients are admitted to hospital. Coordination
between different agencies is a challenge, and emergency services
were often involved because staff in nursing homes or other carers
were concerned about the medico-legal consequences of not seeking
emergency help. The study has enabled Haringey to develop a care
pathway for patients with dementia nearing the end of their lives.
Dr Sampson’s work has highlighted the growing issue of palliative
care for people with dementia. It has fed into the UK’s national strategy
for dementia and informed policy development at the Alzheimer’s
Society. More generally, it has raised awareness of the value of
‘advanced care plans’, in which patients can lay out their wishes and
guide the actions of carers and healthcare and social support teams
as they enter their final days.
Dementia is a devastating condition for patients and for
their carers. The scale of the problem is vast – globally, it
is responsible for 11.2 per cent of years lived with disability
(more than heart disease and cancer combined). In the UK,
annual costs of £17bn are projected to rise to £50bn by 2040.
Dementia is not one of primary care’s strengths, and Professor
Steve Iliffe and colleagues are testing whether an educational
package can improve one important area – early diagnosis.
It is clear that dementia is not being spotted early, for several
reasons. Patients and families may see symptoms of dementia
as typical signs of ageing, or be put off by the enduring stigma
attached to a diagnosis of dementia. Similarly, doctors may
be influenced by the risk of stigmatisation, and may not think
a diagnosis of dementia is in the patient’s best interests.
Moreover, dementia is difficult to assess, and the typical GP
may make only one or two diagnoses a year.
Nevertheless, the benefits of early diagnosis are generally
thought to outweigh these drawbacks. When appropriate,
drug use can be begun earlier, and both families and support
agencies can take steps to prepare for a patient’s inevitable
decline. Even so, an analysis of data in the Health Improvement
Network primary care database found strikingly high mortality
rates, much higher than in community samples, implying late
diagnosis at time of crisis.
To improve early diagnosis, Professor Iliffe’s team tested
three approaches – a CD-ROM, practice-based workshops and
decision-based software – in a randomised controlled trial in
36 practices. Both the workshops and the software significantly
improved detection rates – but had little impact on what GPs
then did.
Following up this encouraging start, the team is now
conducting a second trial, EVIDEM-ED, in 20 practices and
with 200 patients to see if a combination of workshops and
electronic information can go one step further and alter the
clinical management of patients with dementia.
Professor Iliffe was instrumental in developing the early
diagnosis guidelines for the UK’s National Dementia Strategy,
launched in 2009. If the EVIDEM-ED trial is successful it
may point to a way to tackle at least one important aspect of
dementia care.
Sampson EL, Blanchard MR, Jones L, Tookman A, King M. Dementia in the
acute hospital: prospective cohort study of prevalence and mortality. Br J
Psychiatr. 2009;195(1):61–6.
Rait G et al. Survival of people with clinical diagnosis of dementia in
primary care: cohort study. BMJ. 2010;341:c3584.
Watkin L, Blanchard MR, Tookman A, Sampson EL. Prospective cohort study
of adverse events in older people admitted to the acute general hospital: risk
factors and the impact of dementia. Int J Geriatr Psychiatr. 2011. doi: 10.1002/
gps.2693.
Downs M et al. Effectiveness of educational interventions in improving
detection and management of dementia in primary care: cluster
randomised controlled study. BMJ. 2006;332(7543):692-6.
Iliffe S et al. Evidence-based interventions in dementia: A pragmatic
cluster-randomised trial of an educational intervention to promote earlier
recognition and response to dementia in primary care (EVIDEM-ED).
Trials. 2010;11:13.
POPULATION HEALTH UCL School of Life and Medical Sciences
37
A pioneering study of childbirth has become
an equally pioneering study of ageing.
Sixty-five
years young
Babies born in the first
week of March 1946
were particularly special.
They were enrolled in a
groundbreaking study
exploring the factors
contributing to healthy
birth. Remarkably, 65
years later, many of these
infants are still contributing
to science, as part of the
world’s longest running birth
cohort. In between they
have contributed to a host
of influential studies shaping
multiple areas of health
and social policy.
In 1946 there was
considerable concern about
the UK’s declining birth rate,
and the potential impact
of poverty and poor living
conditions. James Douglas,
a doctor noted for his work
on air raid casualties,
was asked to organise a
nationwide study to examine
these factors. At their routine
eight-week follow-up, health
workers across the country
were asked to interview all
mothers who had given
birth during the first week
of March.
Remarkably, for a country
still recovering from the
traumas of the Second World
War, by June 1946 nearly
14,000 mothers had been
interviewed – more than 90
38
per cent of eligible families.
The results were reported
a year later and a book on
the survey, Maternity in
Great Britain, was published
in 1948.
The results painted a
dramatic picture of the
realities of childbirth for
socially disadvantaged
women. Neonatal mortality
was 19 per 1000 births for
the wealthiest families but
30 per 1000 for the poorest.
Less well-off mothers had
lower birthweight babies.
With no NHS backup, the
poorest mothers could not
afford to have a doctor
present at birth, and as few
midwives could administer
gas and air, just 20 per cent
of mothers received any kind
of pain relief during birth.
The shock of this last finding
triggered the first policy
impact – a parliamentary bill
that changed the rules on the
administration of pain relief.
Maternity in Great Britain
was so successful that
funding was rapidly agreed
for a follow up study – 5362
infants becoming part of the
National Survey of Health
and Development. Although
its future has occasionally
been in doubt, the study
has continued ever since,
evolving to shed light
on different questions at
different life stages, with the
Medical Research Council
(MRC) providing funding
since 1962.
The study proved highly
influential. Its findings
changed the way children
were looked after in hospital
and how they were taught
in primary schooling. The
insight it shed on the UK
education system’s failure of
bright children from less well
off families had a particular
profound impact.
In mid-life, work on the
cohort shifted focus, with
an increasing emphasis
on health. Indeed, the
longevity of the cohort has
contributed considerable
insights into ‘life course’
influences on health. Much
of our health is dependent
on the accumulated impact
of past experiences – many
of them carefully recorded
in the cohort records. This
information has provided
an opportunity to see how
participants’ health in later
life has been influenced
by their experiences in
childhood and earlier adult
life. Even what happens
before birth has turned out
to be significant, with the
study providing some of
the first evidence that low
POPULATION HEALTH UCL School of Life and Medical Sciences
birthweight had an impact
on the risk of higher blood
pressure in adult life, as well
as many other aspects of
adult function and chronic
disease risk in later life such
as diabetes. By contrast,
babies of higher birthweight
are at higher risk of
breast cancer.
Sadly, born out of concerns
about the impact of poverty,
the cohort continues
to provide evidence of
the damaging impact of
inequality on health as well
as social opportunities,
providing much material for
the 2010 Marmot Review
(see page 30).
Current research on the
cohort is providing an insight
into ageing – and tying in
early-life events to later life
decline. Most participants
are still going strong, but as
they collectively pass their
65th birthdays the effects
of passing years begin to
tell. The cohort is now the
responsibility of the MRC
Unit for Lifelong Health and
Ageing, led by Professor
Diana Kuh, and forms part of
a multi-cohort collaboration,
HALCyon (Healthy Ageing
across the Life Course),
also led by Professor Kuh.
The nine HALCyon cohorts
collectively include some
Choose your parents well…
The secret to long life, so the joke goes, is to choose your
parents well.
As we age, physical strength becomes a highly significant factor
in health and longevity. Loss of physical capabilities dramatically
reduces quality of life and increases the risk of death, for example
through falls. Work by the MRC Unit for Lifelong Health and Ageing
has shown that lower levels of physical capability (in terms of muscle
strength and physical performance) is associated with a greater risk
of death, and has revealed how factors throughout life – and even
before birth – affect physical capabilities in mid- and later life.
Physical capabilities can be measured relatively easily, by
assessing grip strength, walking speed, the time taken to rise from a
chair and ability to balance while standing. One striking finding has
been the importance of socioeconomic status to these measures, in
childhood as well as adulthood. A father’s occupation and a mother’s
education level both affect later-life physical performance. A metaanalysis carried out under HALCyon confirmed this observation.
Work on the 1946 Birth Cohort was also the first to demonstrate
that childhood growth and development influenced mid-life physical
strength. Other contributing factors include cognitive abilities
(associated with better balance), the timing of developmental
milestones, and physical activity. For men, being married and having
children were associated with higher levels of physical capability.
As well as confirming the long-term impact of socioeconomic
disadvantage on health, the studies also suggest that protection
against frailty in old age could be achieved by promoting physical
fitness decades early.
Cooper R et al. Objectively measured physical capability levels and mortality:
systematic review and meta-analysis. BMJ. 2010;341:c4467. doi: 10.1136/bmj.
c4467.
Kuh D et al. Developmental origins of midlife physical performance: evidence
from a British birth cohort. Am J Epidemiol. 2006;164(2):110–21.
Strand BH, Cooper R, Hardy R, Kuh D, Guralnik J. Lifelong socioeconomic
position and physical performance in midlife: results from the British 1946
birth cohort. Eur J Epidemiol. 2011;26(6):475–83.
Birnie K et al. Childhood socioeconomic position and objectively measured
physical capability levels in adulthood: a systematic review and meta-analysis.
PLoS One. 2011;6(1):e15564.
Guralnik JM et al. Reduced midlife physical functioning among never married
and childless men: evidence from the 1946 British birth cohort study.
Aging Clin Exp Res. 2009;21(2):174–81.
30,000 participants born
between 1918 and 1958.
Much of the success of 1946
Birth Cohort studies has
been down to the excellent
phenotypic data gathered
over such a long period. This
has recently enabled studies
to contribute to large-scale
studies searching for genetic
influences on health. This
adds insight into genetic
as well as environmental
influences. But they also
add a unique life course
dimension, revealing not just
which genetic variants might
be influential but when they
might be influential.
A further exciting emerging
opportunity is the study of
‘epigenetic’ effects – control
of gene activity by chemical
modification of DNA. Indeed,
epigenetic changes may
be one route by which
environmental factors have
a long-term influence on
cells and tissues. Cohort
studies may thus be the
ideal approach for studying
how this interplay between
genes, epigenetics and
the environment shapes
physiology and health
over decades of life.
Kuh D et al. Cohort profile: updating
the cohort profile for the MRC
National Survey of Health and
Development: a new clinic-based
data collection for ageing research.
Int J Epidemiol. 2011;40(1):e1–9.
Pearson H. Study of a lifetime.
Nature. 2011:471;20–4.
POPULATION HEALTH UCL School of Life and Medical Sciences
39
SECTION 5
Global health research
The greatest public health needs lie outside
the UK, particularly in the developing world.
Despite some encouraging progress,
profound global changes – particularly
linked to climate change – threaten to
make a bad situation much worse.
40
POPULATION HEALTH UCL School of Life and Medical Sciences
Resource-poor countries
have traditionally been
blighted by infectious
diseases, some restricted
to tropical areas and others
more globally distributed but
having a disproportionate
impact on less-developed
countries. Infectious
diseases such as HIV/AIDS,
tuberculosis and malaria
(and countless others)
remain key challenges.
But developing countries
also face a second wave of
health threats, linked to major
demographic shifts and
changing lifestyles. Noncommunicable diseases are
becoming of ever greater
importance, particularly in
urban areas – now home to
more than half the world’s
population.
Other causes of illness
and death should not be
overlooked. Road traffic
accidents and injury
(including violent injury)
are major problems. Mental
health problems – predicted
by the WHO to be the
greatest burden of disease
by 2020 – are generally not
well recognised or treated.
Furthermore, developing
countries also find
themselves at the mercy of
global forces over which
they have precious little
control. Climate change
threatens many populations
– from those in low-lying
coastal areas facing greater
saltwater ingression and
An important feature of these trials has been
their participative nature. Rather than plan
interventions in advance, researchers work with
communities to identify key health issues and
ways they might be addressed.
flooding to agricultural
communities dealing with a
greater likelihood of extreme
weather and drought.
Global trade, economics
and politics can all exert
influences that ultimately
affect people’s lives.
Few developing countries
have adequate health
infrastructure. One solution
is to mobilise communities,
creating networks of health
support workers at a local
level. Professor Anthony
Costello and colleagues
have pioneered such an
approach to tackle neonatal
mortality in Asia (see page
43). Randomised clinical
trials have demonstrated
significant benefits, with
interventions that are realistic
and potentially scalable.
The trial in India was
awarded ‘Trial of the Year’
by the Society for Clinical
Trials, which described the
work as an “extraordinary
randomised clinical trial,
conducted with high quality
in a very difficult setting,
and achieving dramatic
results of great public health
importance”.
An important feature of
these trials has been their
participative nature. Rather
than plan interventions
in advance, researchers
work with communities to
identify key health issues
and ways they might be
addressed. Priorities are
thereby established by the
communities themselves,
generating a greater sense
of ownership and increasing
the chances that benefits will
be maintained after the trial.
Further trials are currently
underway in Nepal,
Bangladesh and Malawi.
As well as playing a major
part in these trials, Wellcome
Trust Senior Research Fellow
Dr David Osrin is leading a
programme of research on
the health of slum dwellers in
Mumbai. He has a particular
interest in maternal health
and nutrition, and works
closely with local community
groups and organisations.
UCL also has major research
interests in Africa. One of
the most significant has
been Professor MarieLouise Newell’s involvement
in the Wellcome Trust’s
Africa Centre for Health
and Population Studies in
KwaZulu-Natal, South Africa,
which Professor Newell has
led on secondment from
UCL since 2005. Research
POPULATION HEALTH UCL School of Life and Medical Sciences
41
Zumla has also highlighted
the alarming rise of TB in the
UK – particularly in London,
where the numbers of cases
rose by nearly 50 per cent in
1999–2009.
at the Africa Centre has
revealed much about the
dynamics of HIV infection in
a poor rural community and
the impact of antiviral rollout
programmes.
The Africa Centre has one
of the largest demographic
surveillance systems in
Africa, covering 90,000
people. The area has been
badly affected by HIV: one
in four of the local population
has the virus, including half
of all women aged 25–29;
22 per cent of children have
lost at least one parent to
AIDS. The Centre works
extremely closely with the
local community, playing an
important role in healthcare
delivery as well as research,
and ultimately aims to have
a significant impact on
the spread of HIV locally –
though its research is also
of broader international
significance.
Professor Newell and
colleagues have carried out
influential work on motherto-child transmission of HIV,
including the Mamanengane
trial (‘Mamanengane’
is Zulu for ‘mother and
child’), which showed that
exclusive breastfeeding was
feasible for both infected
and uninfected women,
and resulted in markedly
lower transmission of HIV
to offspring compared to
breastfeeding combined
42
with solid food22. The
study contributed to new
WHO guidelines on infant
feeding. The Centre also
contributed to the landmark
multicentre Kesho Bora
trial, which showed that
antiretrovirals effectively
prevented transmission of
HIV during pregnancy and
breastfeeding.
The Centre has also been
actively involved in the
rollout of antiretrovirals. It has
generated vital evidence that
rollout in poor rural areas
does deliver substantial
health improvements, in
adults and children. The
Centre is also beginning the
‘Treatment as Prevention’
trial, to see if antiretroviral use
can reduce HIV transmission
as well as help patients.
Africa has also been the
main focus of Professor
Alimuddin Zumla, one of
the world’s leading experts
on TB. Professor Zumla is
involved in a wide range
of initiatives centred on
practical methods of HIV
diagnosis and new drug
treatments. He has also
been a tireless advocate
of the need to tackle TB
– responsible for nearly
two million deaths every
year. The disease is not
just a problem in Africa:
it is a major issue in the
restructuring economies of
East Europe, and Professor
Professor Zumla led a Lancet
TB Series, a set of definitive
reviews of key issues around
TB. The series is linked to
the Lancet TB Observatory,
a global initiative addressing
the most important issues in
TB control and treatment. He
has done much to develop
research in his home
country, helping to found
the University of Zambia–
University College London
Medical School (UNZAUCLMS) Research and
Training Project, a regional
centre of excellence linked
to six south African countries
and six in Europe. Long-term
collaborator Dr Peter Mwaba,
recipient of the Royal
Society of Tropical Medicine
and Hygiene’s prestigious
Chalmers Medal in 2005, has
gone on to become Zambia’s
Permanent Secretary in the
Ministry of Health.
TB is also a focus for Dr
Tim McHugh, who is part
of a nationwide consortium
of academic groups, the
UK tuberculosis drug
development consortium
(TBD-UK). Supported by
the MRC, TBD-UK aims
to provide a focus for
increased activity on TB
drug development and
facilitate early stages of
drug development within the
academic environment. TBDUK has identified several
promising chemicals with
anti-TB activity.
Dr McHugh’s team is also
playing an important role in
the Pan-African Consortium
for the Evaluation of
Antituberculosis Antibiotics
(PanACEA), a European–
African initiative organising
clinical trials of new drug
treatments designed
to shorten and simplify
TB treatment. The UCLsponsored REMoxTB trial,
POPULATION HEALTH UCL School of Life and Medical Sciences
one of the largest ever
undertaken in TB treatment,
is assessing whether use
of moxifloxicin can reduce
treatment length from six
to four months. PanACEA
also incorporates two other
trials led from Germany
and The Netherlands, to
which the UCL team is also
contributing.
Capacity building is an
important aspect of the
REMoxTB trial. The REMoxTB
laboratory team has ensured
that laboratories in host
countries are brought up
to international standards
for clinical trials. The UCL
team has also developed a
manual of microbiological
techniques – essential for
work in TB – and trained staff
in their use at participating
sites, an important transfer
of knowledge and skills. As
well as generating important
findings on TB treatment, the
work should also leave the
Africa centres well-placed to
conduct further clinical trials
in the future.
The REMoxTB trial also
involves the MRC Clinical
Trials Unit, which is
embedded within UCL. The
Unit has organised a series
of ground-breaking clinical
trials of HIV treatments in
Africa, led by Professor
Diana Gibb (see page 43).
The DART trial of
antiretrovirals in Uganda
and Zimbabwe, for example,
has shown that it is not
necessary to use hightech equipment to monitor
people on therapy, vitally
important in resource-poor
countries. Moreover, the
trial infrastructure provided
a platform on which other
studies could be added –
creating a suite of DART
projects. As well as HIV drug
therapies, other trials have
tested vaginal microbicidal
22 Coovadia H, Rollins N, Bland R et al.
Mother-to-child transmission of HIV-1
infection during exclusive breastfeeding: the first six months of life. Lancet.
2007;369:1607–16.
DART sharpens practice
Two out of three
Results from the DART trial suggest that laboratory
analysis is not essential to successful HIV treatment –
paving the way for wider roll-out of antiretroviral therapies.
Two large trials have shown that community-based
interventions can significantly reduce neonatal mortality
in poor rural areas.
The past decade has seen a much-needed influx of antiretroviral
drugs into Africa, even if many in need still have little access
to them. As well as availability of affordable drugs, getting
antiretrovirals to patients is difficult in countries with negligible
healthcare infrastructures. Moreover, in developed countries
antiretroviral use is typically guided by CD4 cell numbers, which
requires specialist equipment and regular blood testing to check
for drug side-effects. Yet the DART trial found that, in typical African
settings, laboratory testing for safety provided no benefits and
measuring CD4 counts offered only minimal benefits at significant
additional cost – which, in budget-limited times, could be better
spent on improving access to antiretrovirals.
The DART (Development of Antiretroviral Therapy) trial
compared treatment based on either laboratory testing of CD4
counts or clinical assessment in more than 3000 HIV-infected adults
commencing antiretroviral therapy in Uganda and Zimbabwe.
Coordinated by the MRC Clinical Trials Unit, DART was the largest
trial of antiretrovirals ever carried out in Africa.
Survival in both arms of the trial was remarkably good – in the
laboratory tests arm, 90 per cent of patients were still alive after
five years, as were 87 per cent of patients managed clinically.
The difference between the two groups only appeared in later
years, and probably reflected switching of patients onto second-line
drugs in the laboratory tests arm, after drops in CD4 cell numbers
provided warning signs of first-line treatment failure.
However, given the economic and practical difficulties involved in
laboratory testing, this small difference could be greatly outweighed
by the potential benefits of treating more patients. Health economic
analyses suggest that, for the same investment needed to achieve
laboratory testing, the numbers of patients treated could be
increased by about a third.
Professor Anthony Costello and colleagues have pioneered
an inclusive, participatory approach to the development of
interventions to improve neonatal health. Large-scale trials in Nepal
and India have been highly successful, reducing neonatal mortality
by up to 45 per cent. The failure of a trial in Bangladesh was
therefore disappointing, but may have identified some of the factors
critical to the success of this approach.
Nearly 4 million neonatal deaths occur each year, 98 per cent
of them in the developing world. Reducing this number is essential
if Millennium Development Goal 4, reducing child mortality by
two-thirds, is to be met.
However, the challenge is daunting. In rural areas, health service
infrastructures are limited and mothers have little access
to trained antenatal healthcare. Interventions have to recognise
these constraints and consider issues such as sustainability –
will changes be maintained after the trial – and scalability: could an
intervention be applied to larger populations.
Professor Costello’s group has developed a distinctive bottom-up
and participatory approach. Rather than descend on populations
with ready-planned interventions, his team works with community
groups to identify key health issues and potential solutions.
The effectiveness of these interventions is then tested in
randomised trials.
Using this approach, the UCL team has worked with women’s
groups to develop low-cost interventions which achieved excellent
results in Nepal – reducing neonatal mortality by 30 per cent.
A similar strategy was even more successful in two regions of India,
cutting neonatal deaths by 45 per cent in a high-mortality area.
These dramatic success stories are tempered by the results from
a study in Bangladesh, which failed to achieve any improvement in
mortality rates. The failure may, however, highlight important factors
necessary for successful interventions. In Bangladesh, the women’s
groups covered larger populations, and group coordinators had
more groups to coordinate. Local factors, such as adverse weather
conditions, may also have affected the effectiveness of the delivery
of the intervention.
Collectively the studies suggest that women’s group could play
an important role in neonatal healthcare in the developing world.
However, particular care needs to be given to how interventions are
developed and implemented to ensure they are successful.
Mugyenyi P et al. Routine versus clinically driven laboratory monitoring of
HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.
Lancet. 2010;375(9709):123–31.
Manandhar DS et al. Effect of a participatory intervention with women’s
groups on birth outcomes in Nepal: cluster-randomised controlled trial.
Lancet. 2004;364:970–9.
Tripathy P et al. Effect of a participatory intervention with women’s groups on
birth outcomes and maternal depression in Jharkhand and Orissa, India: a
cluster-randomised controlled trial. Lancet. 2010;375(9721):1182–92.
Azad K et al. Effect of scaling up women’s groups on birth outcomes in three
rural districts in Bangladesh: a cluster-randomised controlled trial. Lancet.
2010;375(9721):1193–202.
POPULATION HEALTH UCL School of Life and Medical Sciences
43
Climate change threatens to have a
disproportionate effect on the world’s poorest
(and, ironically, those who have contributed least
to it).
gels and a prototype HIV
vaccine. Ongoing trials
include ARROW, comparing
first-line treatments for
children with HIV, and
EARNEST, which aims to
identify the best second-line
options in resource-poor
settings.
Is a bolus the best?
A clinical trial in Africa has raised serious questions
about a routinely used treatment for severe shock
in children.
The symptoms of severe shock are all too common in African
children, typically associated with malaria or bacterial infection.
In the developed world, infants in shock are rapidly given
rehydrating fluids in a single intravenous shot or ‘bolus’. Smallscale (but uncontrolled) trials in Africa had suggested that
a similar approach might also be beneficial in low-resource
setting. But a large, multicentre, randomised controlled trial
organised by Professor Kath Maitland at the Wellcome Trust–
KEMRI Research Programme, Kilifi, Kenya, and Professor
Diana Gibb and colleagues from the MRC Clinical Trials Unit
was stopped early when it became clear that the fluid bolus was
actually increasing mortality compared with giving fluids slowly
– raising major questions about the procedure in rich as well
as poor countries.
The study, carried out in six hospitals in Kenya, Tanzania and
Uganda, compared two different types of bolus infusion – saline
and albumin solution – with no infusion. Otherwise, children
received WHO-recommended standards of emergency care.
Recruitment was based on symptoms – the underlying causes of
severe shock are rarely known on admission to hospital – though
children with malnutrition or gastroenteritis were excluded.
The study was halted after around 3000 infants had been
treated, when it became clear that an extra three to four deaths
occurred within 48 hours for every 100 children given a bolus.
Of note, the clinical systems used in the trial actually resulted
in better survival rates overall. Survival rates of between 80–85
per cent are typical in African children with shock, whereas in
this study 89.4 per cent of those given boluses survived the first
48 hours in hospital. Children given fluids more slowly did even
better, however, with 92.7 per cent surviving.
The results are disappointing but imply that rapid fluid
resuscitation for shock is not advisable in resource-poor
settings. The reasons are unclear, underlining the current
limited understanding of shock. Furthermore, the findings raise
questions about fluid management in the developed world,
where fluid resuscitation is believed to have contributed to a
major reduction in paediatric deaths from septic shock but has
never been formally assessed in a randomised controlled trial.
Maitland K et al. Mortality after fluid bolus in African children with severe
infection. New Engl J Med. 2011;364(26):2483–95.
44
Other studies have focused
on prevention. In Zimbabwe,
Dr Frances Cowan and
colleagues have carried out
one of the world’s largest
trials of a behavioural
intervention. The trial failed
to achieve any lasting
impact on HIV transmission,
illustrating just how hard it
can be to alter behaviour.
The Africa Centre has noted
a similar phenomenon,
with HIV transmission rates
remaining stubbornly high.
Diversity
Beyond infectious disease,
UCL researchers are
exploring a diverse range of
international health issues.
Professor Therese Hesketh,
for example, is one of the
UK’s leading experts on
healthcare in China. She
has been leading a major
project, funded by the UK
Department for International
Development, which aims
to address inequalities in
access to medicines in
rural areas of China with a
total population of around
15 million people. Professor
Hesketh’s previous work has
identified high levels of stress
in China’s highly pressured
primary schools23. She has
also drawn attention to the
excess numbers of boys
and sex-selective abortion in
China24. In 2005, there were
32 million more boys than
girls under 20.
POPULATION HEALTH UCL School of Life and Medical Sciences
Professor Nora Groce, an
anthropologist formerly at
Yale University, is leading
a programme of work on
disability and social inclusion
in the developing world. An
adviser to the WHO, UNICEF
and UNFPA, Professor
Groce was guest editor of a
special issue of the Lancet
dedicated to disability.
Epidemiologist Dr David
Batty is carrying out a
wide range of analyses of
data from the UK, Europe
and further afield. He has
examined associations
between adult obesity and
cancer mortality in more
than 400,000 participants
from Asia, Australia and New
Zealand. Although data are
scarce in Asia, overweight
and obese individuals in
populations across the
Asia-Pacific region have a
significantly increased risk of
mortality from several types
of common cancers. Dr Batty
is also studying risk factors
for suicide in more than one
million adults in South Korea,
which has one of the world’s
highest suicide rates.
Although child mortality
remains desperately high
in many countries, some
progress has been made.
But there is also evidence
that premature death of older
children and young adults
is not receiving the attention
it deserves. Using WHO
figures, Professor Russell
Viner and colleagues in
Australia and Switzerland
found that, of 2.6 million
deaths in young people aged
10–24 years in 2004, 97 per
cent were in the developing
world25. Deaths rate were
particularly high in older
age groups and although
causes varied by sex,
age and region, maternal
conditions, traffic accidents
and violence were all having
an impact on the same scale
as the classic infectious
diseases.
The global environment
The future health of many
communities is intimately
bound up with global ‘big
issues’ – climate change,
international trade, migration
and urbanisation, and
population growth. Reflecting
these profoundly important
issues, UCL’s global health
research is increasingly
multidisciplinary.
In 2009, the UCL–Lancet
Commission on Managing
the Health Effects of Climate
Change described climate
change as ‘the biggest global
health threat of the 21st
century’. The commission,
which drew on UCL expertise
in 19 different units, including
law, anthropology, politics,
economics and engineering
as well as public health and
international development,
drew attention to the current
health impact of climate
change, as well as its
potential future catastrophic
effects26.
Climate change threatens
to have a disproportionate
effect on the world’s poorest
(and, ironically, those who
have contributed least
to it). The commission
recommended framing
climate change in terms
of its health impact, to
galvanise decision-makers
and promote action across
a number of domains to limit
carbon consumption and
to encourage adaptation.
The Commission called for a
‘collation of global expertise’
and a new multidisciplinary
and multisectoral public
health movement to
coordinate thinking and
action across governments,
international agencies,
NGOs, and academic
institutions.
In related work, Yvonne
Rydin, Professor of Planning,
Environment and Policy,
is leading an initiative on
‘Healthy Cities’, which is
assessing how changing
the built environment might
affect the health of residents.
This ranges from examining
community-led sanitation
projects in Mumbai to how
social housing might affect
mental health in London.
Links between urban
development, climate change
and sustainable cities are
an important theme.
Economic perspectives are
provided by such luminaries
as Professor Costas Meghir
and Professor Orazio
Attanasio. With economist
Dr Noemi Pace, Professor
Costello has highlighted how
speculative investment in
food commodity derivatives
can disrupt the supply of
food to meet human needs27.
UCL organises a wide range
of events linked to global
health. In May 2011, with
funding from the Leverhulme
Trust, it hosted a symposium
on ‘Population Footprints:
Challenging debates
on popular, gender and
development’. The event
brought together groups that
might not normally interact,
including researchers, policy
makers and advocates from
a broad range of fields.
Almost 300 delegates
took part, representing 33
countries, and a satellite
meeting, with 100 delegates,
was held in Kenya. The
initiative also included a
public event, and follow-up
public engagement activities.
23 Hesketh T et al. Stress and psychosomatic symptoms in Chinese school
children: cross-sectional survey. Arch
Dis Child. 2010;95(2):136–40.
24 Zhu WX, Lu L, Hesketh T. China’s excess males, sex selective abortion, and
one child policy: analysis of data from
2005 national intercensus survey. BMJ.
2009;338:b1211.
25 Viner RM et al. 50-year mortality
trends in children and young people: a
study of 50 low-income, middle-income,
and high-income countries. Lancet.
2011;377(9772):1162–74.
26 Costello A et al. Managing the health
effects of climate change: Lancet and
University College London Institute
for Global Health Commission. Lancet.
2009;373(9676):1693–733.
27 Pace N, Seal A, Costello A.
Food commodity derivatives:
a new cause of malnutrition?
Lancet. 2008;371(9625):1648–50.
POPULATION HEALTH UCL School of Life and Medical Sciences
45
Population Health research at UCL
Component institutes
Most of the population health research at UCL is carried
out by groups within the UCL Faculty of Population
Health Sciences, which comprises:
• UCL Institute of Epidemiology and Health Care
• UCL Institute of Child Health
• UCL Institute for Women’s Health The broader Population Health Domain at UCL
encompasses researchers across the whole of the
UCL School of Life and Medical Sciences, as well as
individuals with relevant interests outside the School.
Domain Chair: Professor Anne Johnson
www.ucl.ac.uk/slms/domains/population-health
• UCL Institute of Cardiovascular Science
Dean: Professor Graham Hart
www.ucl.ac.uk/populationhealth-sciences/
UCL in London
Partners
Researchers in the UCL School of Life and Medical
Sciences occupy a range of buildings on UCL’s central
Bloomsbury Campus, at the nearby Royal Free Hospital
and Whittington Hospital/Archway Campus sites,
and other central London locations.
UCL School of Life and Medical Sciences works closely
with a range of local, national and international partners.
Of particular significance are its close links to local NHS
bodies, collectively forming UCL Partners, one of just
five UK Academic Health Science Centres. These links
underpin UCL’s NIHR Biomedical Research Centres
at UCLH, the UCL Institute of Child Health (with Great
Ormond Street Hospital) and the UCL Institute
of Ophthalmology (with Moorfields Eye Hospital).
1 UCL Main Campus
2 UCL Hospital
3 Great Ormond Street Hospital and
UCL Institute of Child Health
4 Moorfields Eye Hospital and
UCL Institute of Ophthalmology
5 Royal Free Hospital and UCL School of Medicine
6 Whittington Hospital and Archway Campus
With the MRC, Wellcome Trust and Cancer Research
UK, UCL is also a founding partner of the Francis Crick
Institute, led by Professor Sir Paul Nurse, which is due
to open in 2015.
UCL also establishes wider partnerships in the UK,
for example with Imperial College to set up the London
Centre for Nanotechnology, and with Imperial, King’s
College London, the MRC and GlaxoSmithKline on the
‘Imanova’ clinical imaging initiative. The agreement
was forged under the umbrella of the Global Medical
Excellence Cluster (GMEC), a public–private partnership
bringing together world-leading academic, health and
industrial partners in South-East England.
6
5
2 1 4
3
46
The School has also developed ties with nearby academic
centres, including the London School of Hygiene and
Tropical Medicine and Birkbeck College. As well as many
joint research initiatives, the institutions also liaise at a
strategic level.
London As well as numerous international research collaborations,
UCL has developed a strategic alliance with Yale
University, the Yale–UCL Collaborative, to promote
cross-fertilisation and joint ventures across education,
research and application.
POPULATION HEALTH UCL School of Life and Medical Sciences
Support: Resource centres and platforms
Research income
The scale of UCL’s research enables it to provide a range
of technical infrastructure platforms to support research.
These include outstanding facilities and technical expertise
in molecular and cellular imaging, as well as pre-clinical
and clinical imaging, and several sites specialising in
high-throughput sequencing and genome analysis.
‘Live’ grants as at 1 September 2011
Other core platform technologies cover small-chemical
libraries, proteomics, biological services and transgenics,
and informatics. UCL researchers are also involved in
numerous biobanking initiatives and cohort studies,
providing access to extensive collections of materials
and data.
UCL also provides capital infrastructure funding to
enable labs to develop their equipment base.
For clinical research, a Research Support Centre
provides access to essential support for work on people
and patients, including liaison with the UCLH/UCL NIHR
Biomedical Research Centre, UCL Clinical Trials Unit
and UCLH/UCL Clinical Research Facility.
The Translational Research Office works to promote the
translation of research into therapies, techniques and
products with therapeutic value.
www.ucl.ac.uk/platforms/
www.ucl.ac.uk/slms/research_support_centre
NIHR and other UK Government
£177.1m
MRC
£194.6m
Other UK Research Councils
UK charities
£83.3m
£500.4m
£53.6m
Commercial (UK and international)
EU£78.4m
£62.6m
Other international, inc. NIH
Other£14.7m
Total£1164.7m
Figures refer to research within the UCL School of Life and Medical Sciences.
NIHR: National Institute for Health Research; MRC: Medical Research Council;
NIH: National Institutes of Health.
UCL Grand Challenges
UCL is committed to developing wise and timely counsel
to address significant intellectual, cultural, scientific,
economic, environmental and health problems.
The UCL Grand Challenges – of Global Health,
Sustainable Cities, Intercultural Interaction and Human
Wellbeing – facilitate collective, collaborative working
practices in order to gain fresh perspectives and address
aspects of the world’s key problems in their full complexity.
We are also intent on making the resulting conclusions
compelling to policy makers and practitioners.
POPULATION HEALTH UCL School of Life and Medical Sciences
47
Sponsors of research
We are grateful to all the individuals and organisations who support
research in the UCL School of Life and Medical Sciences.
Abbott France, Abbott Laboratories, Ablynx NV, Academy of Medical Sciences,
Action Medical Research, Action on Hearing Loss, Adam Dealy Foundation,
Against Breast Cancer, Age UK (Formerly Research Into Ageing), Agennix AG,
Aims 2 Cure, Alcohol Education and Research Council, Alder Hey Children’s NHS
Foundation Trust, Alexion Pharmaceuticals, Allergan Inc., Alpha-1 Foundation,
Alzheimer’s Society, Alzheimer’s Research UK, Amyotrophic Lateral Sclerosis
Association, Anatomical Society of Great Britain & Ireland, Anna Freud Centre,
Anthony Nolan Bone Marrow Trust, Apatech Ltd, Apitope Technology (Bristol) Ltd,
Aqix Ltd, Argonne National Laboratory, Ark Therapeutics Ltd, Arthritis Research
UK, Arts and Humanities Research Council, Assisted Conception Unit, Association
for International Cancer Research, Association Francaise Contre les Myopathies,
Association Monegasque Contre Les Myopathies, Association of Coloproctology
of Great Britain and Ireland, Asthma UK, Astra Zeneca (UK) Ltd, Ataxia UK,
Autonomic Disorders Association – Sara Matheson Trust, AVI BioPharma Inc.,
AXA Research Fund, Bachmann-Strauss Dystonia and Parkinson Foundation,
Baily Thomas Charitable Trust, Baily Thomas Charitable Trust, Barts and The
London Charity, Batten Disease Family Association, Baxter Healthcare Corp.,
Bayer – AG, Bayer SAS, Big Lottery Fund, Bill & Melinda Gates Foundation,
Biochemical Society, Biocompatibles Ltd, Biogen, Biogen Idec Inc., Biomarin
Pharmaceutical Inc., Biorex R&D, Biotechnology and Biological Sciences
Research Council, Birkbeck College, Biss Davies Charitable Trust, Boehringer
Ingleheim, Bone Cancer Research Trust, Brain Research Trust, Breast Cancer
Campaign, Bristol Myers Squibb, British Academy, British Council for Prevention
of Blindness, British Heart Foundation, British HIV Association, British Lung
Foundation, British Medical Association, British Neurological Research Trust,
British Orthodontic Society, British Pharmacological Society, British Psychological
Society, British Retinitis Pigmentosa Society, British Skin Foundation, British
Society for Haematology, British Tinnitus Association, British Urological
Foundation, BUPA Foundation Medical Research Charity, Burdett Trust for
Nursing, Burroughs Wellcome Fund, Cambridge University Hospital NHS
Foundation Trust, Camden and Islington Health Authority, Canadian Institutes of
Health Research, Cancer Fund, Cancer Research Institute USA, Cancer Research
UK, Carbon Trust Ltd, Carl Zeiss Surgical GMBH, Celera Corp., Cell Medica Ltd,
Centocor Inc., Central and East London CLRN, Central Research Fund, Cephalon
Inc., Charles Wolfson Charitable Trust, Chemel AB, Child Growth Foundation, Child
Health Research Appeal Trust, Children Living with Inherited Metabolic Diseases
(CLIMB), Children With Cancer UK, Children’s Brain Diseases, Children’s Cancer
and Leukaemia Group, Children’s Liver Disease Foundation, Children’s Research
Fund, Children’s Trust, Chordoma Foundation, Chronic Fatigue Syndrome
Research Foundation, Chronic Granulomatous Disease Trust, Chugai Pharma
Europe Ltd, Cincinnati Children’s Hospital Medical Center, Circulation Foundation,
CLEFT – Bridging The Gap, Clement Wheeler Bennett Trust, CMT UK, Cobra
Bio-Manufacturing PLC, Cochlear Research and Development Ltd, Coda
Therapeutics Inc., Cogent (Holdings) Ltd, Colgate-Palmolive Europe, College of
Optometrists, Colt Foundation, Creating Resources for Empowerment and Action
Inc., Cure Parkinson’s Trust, Cure PSP – Society for Progressive Supranuclear
Palsy, Cyberonics Inc., Cystic Fibrosis Research Trust, Cystinosis Foundation
Ireland, Cystinosis Research Network Inc., David and Elaine Potter Charitable
Foundation, Davis Schottlander & Davis Ltd, Deafness Research (Formerly
Defeating Deafness), Defense Advanced Research Projects Agency, Department
for Children, Schools and Families, Department for Education and Skills,
Department for International Development, Department of Health, Department of
Health and Human Services, Department of Trade and Industry, Dermatitis and
Allied Diseases Research Trust, Deutsche Forschungsgemeinschaft, Diabetes
Research and Wellness Foundation, Diabetes UK, Diagenode SA, Doctors
Laboratory, Dowager Countess Eleanor Peel Trust, Duchenne Parent Project,
Dystonia Medical Research Foundation, Dystrophic Epidermolysis Bullosa
Research Association, East Midlands Specialised Commissioning Group,
Economic and Social Research Council, Edinburgh University, Edmond J Safra
Philanthropic Foundation, Effort – Eastman Foundation, Efic, Eisai (London)
Research Laboratories Ltd, El.En. S.p.A, Elan Pharmaceuticals Ltd, Eli Lilly and
Co. Ltd, Emergency Nutrition Network, Engineering and Physical Sciences
Research Council, Epic Database Research Company Ltd, Epilepsy Action,
48
Epilepsy Research UK, Eular – European League Against Rheumatism,
Eurocoating S.P.A, European and Developing Countries Clinical Trials, European
Association for the Study of Liver, European Commission, European Huntington’s
Disease Network, European Organisation For Research and Treatment of Cancer,
European Orthodontic Society, European Parliament, European Respiratory
Society, European Society for Immunodeficiencies, Eve Appeal, Experimental
Psychology Society, F Hoffmann La Roche Ltd, Fidelity Foundation, Fight For Sight,
Fondation de France, Food Standards Agency, Foundation for Fighting Blindness,
Foundation for Liver Research, Foundation for the Study of Infant Deaths,
Foundation Leducq, Frances and Augustus Newman Foundation, Frost Charitable
Trust, Fundacao Bial, Gatsby Charitable Foundation, Gen-Probe Life Sciences Ltd,
Genentech Inc., General Charitable Trust of ICH, General Medical Council,
Genethon, Genex Biosystems Ltd, Genzyme Corp., Gilead Sciences Inc.,
GlaxoSmithKline, Glaxosmithkline (China) R&D Co. Ltd, Global Alliance for TB
Drug Development, Government Communications Planning Directorate, Great
Britain Sasakawa Foundation, Great Ormond Street Hospital Charity, Great
Ormond Street Hospital Special Trustees, Grifols UK Ltd, Grovelands Priory
Hospital, Grunenthal GMBH, Guarantors of Brain, Guide Dogs for the Blind
Association, Gynaecological Cancer Research Fund, H J Heinz Co. Ltd, Harbour
Foundation, Health and Safety Executive, Health Foundation, Health Protection
Agency, Healthcare Commission, Healthcare Quality Improvement Partnership,
Heart Research UK, Helpage International – Africa Regional Development, Henry
Smith Charity, Hestia Foundation, High Q Foundation, Histiocytosis Research
Trust, Hospital For Sick Children, Human Early Learning Partnership, Human
Frontier Science Program, Human Genome Sciences Inc., Huntington’s Disease
Association, Ichthyosis Support Group, Illumina Cambridge Ltd, Imperial College
Consultants Ltd, Imperial College of Science, Technology and Medicine, Inhibox
Ltd, Institut de Recherche Servier, Institut Straumann AG, Instrumentarium Science
Foundation, Intensive Care Society, International Association for the Study of Pain,
International Balzan Foundation, International Child Development Programme,
International Glaucoma Association, International Primary Care Respiratory Group,
International Serious Adverse Events Consortium, International Spinal Research
Trust, Ipsen Fund, Ipsen Ltd, Iqur Ltd, ISTA Pharmaceuticals, ITI Foundation,
Jabbs Foundation, James S McDonnell Foundation, James Tudor Foundation,
Janssen Pharmaceutica NV, Janssen-Cilag Ltd, Japan Society for the Promotion
of Science, Jean Corsan Foundation, Jerini Ophthalmic Inc., John Templeton
Foundation, John Wyeth & Brother Ltd, Johns Hopkins University, Johnson &
Johnson Consumer Services EAME Ltd, Juvenile Diabetes Foundation, Katherine
Dormandy Trust, Kay Kendall Leukaemia Fund, Kidney Research UK, Kids
Company, Kids Kidney Research, King’s Fund, King’s College London, Legal and
General Assurance Society Ltd, Leonard Cheshire Disability, Leukaemia and
Lymphoma Research, Leverhulme Trust, Lincy Foundation, Linkoping University,
Linnean Society of London, Lister Institute of Preventive Medicine, Liver Group,
London Borough of Camden, London Deanery, London School of Hygiene and
Tropical Medicine, Lowe Syndrome Trust, Lowy Medical Research Institute,
Ludwig Institute for Cancer Research, Lund University, Lupus UK, Lymphoma
Research Trust, Macmillan Cancer Relief (UK Office), Macular Disease Society,
Marc Fisher Trust, Marie Curie Cancer Care, Mars Symbioscience, Mary Kinross
Charitable Trust, Mason Medical Research Foundation, Matt’s Trust Fund for
Cancer, Maurice Hatter Foundation, Max Planck Institute for Molecular Genetics,
Max Planck Institute of Biology and Ageing, Medac GmBH, Medical Research
Council, Medical Research Council of Canada, Medical Research Foundation,
Melford Charitable Trust, Mend Central Ltd, Meningitis Research Foundation,
Meningitis Trust, Merck Ltd, Merck Serono, Mermaid, Michael and Morven Heller
Charitable Foundation, Michael J Fox Foundation for Parkinson’s Research,
Middlesex Hospital Special Trustees, MIND, Mologic Ltd, Monument Trust,
Moorehead Trust, Moorfields Eye Hospital (LORS), Moorfields Eye Hospital
Development Fund, Moorfields Eye Hospital Special Trustees, Moorfields Hospital
NHS Foundation Trust, Motor Neurone Disease Association, Moulton Charitable
Trust, Mr and Mrs Fitzpatrick, MRCP(UK), MSS Research Foundation, Multiple
Sclerosis International Federation, Multiple Sclerosis Society of Great Britain and
Ireland, Mundipharma Research Ltd, Muscular Dystrophy Association, Muscular
Dystrophy Campaign, Myasthenia Gravis Association, Myeloma UK, National
Association for Colitis and Crohn’s Disease, National Brain Appeal, National
Cancer Institute, National Centre for Social Research, National Centre for the
POPULATION HEALTH UCL School of Life and Medical Sciences
Replacement, Refinement and Reduction of Animals in Research, National Contest
for Life, National Eye Institute, National Geographic, National Health and Medical
Research Council, National Institute for Health and Clinical Excellence, National
Institute for Health Research, National Institute of Academic Anaesthesia, National
Institute of Mental Health, National Institutes of Health, National Kidney Research
Fund, National Multiple Sclerosis Society, National Osteoporosis Society, National
Screening Committee, Natural Environment Research Council, NCL Stiftung,
Netherlands Organisation for Scientific Research, Neuroblastoma Society,
New England Research Institutes Inc., Newlife Foundation For Disabled Children,
NHS Blood and Transplant, NHS Executive, NHS Patient Safety Research
Programme, Nicholls Foundation, Nicox SA, NIHR School of Primary Care
Research, Nippon Telegraph and Telephone Corporation, No Surrender Charitable
Trust, Nobel Biocare AB, North Essex Mental Health Partnership NHS Trust,
Northern California Institute for Research and Education, Novartis Pharma AG,
Novartis Pharmaceuticals Corp., Novartis Pharmaceuticals UK Ltd, Novo Nordisk
Pharmaceuticals Ltd, Nuffield Foundation, Ocean Park Conservation Foundation,
Ocera Therapeutics Inc., Octapharma, Office for National Statistics, Options
Consultancy Services Ltd, Organisation for the Understanding of Cluster
Headache, Organon Laboratories Ltd, Orphan Europe (UK) Ltd, Ovarian
Cancer Action, Overweight and Heart Diseases Research Trust, Oxalosis
and Hyperoxaluria Foundation, Oxford Optronix Ltd, Oxigene Inc., Ozics OY,
Paediatric Rheumatology Discretionary Fund, Palaeontological Association,
Pancreatic Cancer UK, Parkinson’s Disease Society, Path Vaccine Solutions,
Pathogen Solutions UK Ltd, Pathological Society of Great Britain and Ireland,
Paul Hamlyn Foundation, PCI Biotech, Pelican Cancer Foundation, Peptide Protein
Research Ltd, Pervasis Therapeutics Inc., Peter Samuel Fund, Petplan Charitable
Trust, Pfizer Ltd, Philips Medical Systems NL BV, Philips Oral Healthcare Inc.,
Physiological Society, Planer Plc, Polycystic Kidney Disease Charity, Primary
Immunodeficiency Association, Procter and Gamble Technical Centre Ltd,
Progressive Supranuclear Palsy (PSP Europe) Association, Prostate Action,
Prostate Cancer Research Centre, PTC Therapeutics Inc., Qatar National
Research Fund, Race Equality Foundation, Rank Bequest, Raymond and Beverly
Sackler Foundation, Raynaud’s and Scleroderma Association, Repregen Ltd,
Research in Motion Ltd (Canada), Research into Childhood Cancer, Rheumatology
Discretionary Fund, Rho Inc., RMS Innovations UK Ltd, Roche Bioscience, Roche
Products Ltd, Rockefeller Foundation, Roddick Foundation, Ronald McDonald
House Charities UK, Rosetrees Trust, Roslin Cells Ltd, Royal Academy of
Engineering, Royal Centre for Defence Medicine, Royal College of Anaesthetists,
Royal College of General Practitioners, Royal College of Ophthalmologists, Royal
College of Paediatrics, Royal College of Physicians, Royal College of Radiologists,
Royal College of Surgeons of England, Royal Free Cancer Research Trust, Royal
Free Hampstead NHS Trust, Royal Free Hospital Special Trustees, Royal National
Institute for the Blind, Royal Society, Samantha Dickson, Sanofi Pasteur,
Sanofi-Aventis, Santhera Pharmaceuticals Ltd, Sarah Cannon Research UK Ltd,
Sarcoma Alliance for Research Through Collaboration, Save The Children, Science
and Technology Facilities Council, Scope International AG, Selcia Ltd, Sheffield
Teaching Hospitals NHS Foundation Trust, Shire Human Genetic Therapies AB,
Siemens plc, Sir Halley Stewart Trust, Sir Jules Thorn Charitable Trust,
Skeletal Cancer Action Trust Plc, SMA Trust, Smith & Nephew Plc, Society for
Endocrinology, Society for Pediatric Radiology, Sport Aiding Medical Research
For Kids (SPARKS), St George’s Hospital Medical School, St Peter’s Research
Trust, Stanford University, Stanley Medical Research Institute, Stanley Thomas
Johnson Foundation, Stanmore Implants Worldwide Ltd, Stroke Association,
Sue Harris Bone Marrow Trust, Summit plc, Supreme Biotechnologies Ltd, Susan G
Komen Breast Cancer Foundation, Swiss National Science Foundation, Syngenta,
Sysmex Ltd, Takeda Cambridge Ltd, Takeda Europe Research and Development
Centre Ltd, Takeda Pharmaceutical Co. Ltd, Tana Trust, Target Ovarian Cancer,
Tavistock and Portman NHS Trust, Tavistock Trust for Aphasia, Technology and
Medicine, Technology Strategy Board, Teenage Cancer Trust, Thomas Pocklington
Trust, Thrombosis Research Institute, Tissue Regenix Group Plc, Tourette
Syndrome Association Inc., Toyota Motor Europe, Tuberous Sclerosis Association
of Great Britain, UBS AG, UCB Pharma SV, UCB S.A, UCLH/UCL Comprehensive
Biomedical Research Centre, UK Clinical Research Collaboration, UK Human
Tissue Bank, UK Stem Cell Foundation, Unilever UK Central Resources Ltd, United
Kingdom Continence Society, United Therapeutics Corporation, University College
London Hospitals, University College London Hospitals Charities, University
Medical Center Hamburg–Eppendorf, University of Alabama at Birmingham,
University of California, University of Coimbra, University of Iowa, University of
Kansas Medical Center, University of Kwazulu-Natal, University of London,
University of Oulu, University of Oxford, University of Rochester, University of
Southampton, University of Sussex, University of Washington, University of
Western Australia, Varian Ltd, Ventana Medical Systems Inc., Veterinary
Laboratories Agency, Vitaflo International Ltd, Vital Therapies Inc., Vitol Charity
Fund, Wayne State University, Weight Concern, Weizmann UK, Wellbeing of
Women, Wellchild, Wellcome Trust, Welton Foundation, Wockhardt UK Ltd, Wolfson
Foundation, World Cancer Research Fund, World Health Organization, World
Vision International, Wyeth Laboratories and Wyeth Pharmaceuticals Inc.
CREDITS
Commissioned photography: David Bishop (pages 7, 19, 22, 25, 26, 34, 37).
Other images from UCL/UCLH collections except cover: iStockphoto/
CEFutcher; page 2: iStockphoto/Paha_L; page 4: iStockphoto/Brosa;
page 5: iStockphoto/Mishatc; page 6: iStockphoto/Reynardt; pages 7, 8:
iStockphoto/Rubberball; page 8: iStockphoto/nano; page 9: CNRI/Science
Photo Library; page 10: iStockphoto/RapidEye; page 11: Ian Jones; pages
12–13: iStockphoto/stuartbur; page 13: iStockphoto/sonicken; page 13:
iStockphoto/RapidEye; page 14: iStockphoto/sjlocke; page 15: Mary Evans
Picture Library/Roger Mayne; page 16: Krista Kennell/ZUMA/Corbis; page 17:
iStockphoto/Juanmonino; page 18: Jean-Yves Sgro/Visuals Unlimited/Corbis;
page 18: iStockphoto/Kuzma; page 19: iStockphoto/Blend_Images; page
20: iStockphoto/Photo_Concepts; page 21: iStockphoto/skynesher; page 22:
iStockphoto/AndreasKermann; page 23: iStockphoto/mimal; page 24: Paul
Griggs, Wellcome Images; page 24: Anna Tanczos, Wellcome Images; page
26: PBNJ Productions/Corbis; page 27: Wellcome Images; page 27: Justine
Desmond, Wellcome Images; page 28: Ed Kashi/Corbis; page 28: iStockphoto/
sjlocke; page 29: iStockphoto/surpasspro; pages 30–31: Peter Macdiarmid/
Getty Images; page 32: iStockphoto/Yuri_Arcurs; page 33: Punchstock; page
34: iStockphoto/Falcon76; page 35: iStockphoto/DavorLovincic; page 36:
istockphoto/monkeybusinessimages; page 36: Najlah Feanny/Corbis; page
37: iStockphoto/AlexRaths; page 38: iStockphoto/filizturkseven; page 40:
iStockphoto/guenterguni; page 41: Frederic Soltan/Corbis; page 42: Africa
Centre for Health and Population Studies; page 43: Clive Chilvers, Wellcome
Images; pages 43, 45: iStockphoto/hadynyah; page 44: John Stanmeyer/VII/
Corbis; page 45: Nyani Quarmyne/Aurora Photos/Corbis.
Text: Ian Jones, Jinja Publishing Ltd
Design: Jag Matharu, Thin Air Productions Ltd
© UCL. Text may not be reproduced without permission. The UCL ‘dome’ logo
and the letters ‘UCL’ are the registered trademarks of UCL and may not be
used without permission.
TAP1345/16-12-11/V8
POPULATION HEALTH UCL School of Life and Medical Sciences
49
About UCL
Founded in 1826, UCL was the first English university
established after Oxford and Cambridge, the first to
admit students regardless of race, class, religion or
gender, and the first to provide systematic teaching
of law, architecture and medicine. UCL is among the
world’s top universities, as reflected by performance
in a range of international rankings and tables. Alumni
include Marie Stopes, Jonathan Dimbleby, Lord Woolf,
Alexander Graham Bell, and members of the band
Coldplay. UCL currently has over 13,000 undergraduate
and 9,000 postgraduate students. Its annual income is
over £700 million.
www.ucl.ac.uk
UCL
Gower Street
London WC1E 6BT
Tel: +44 (0)20 7679 2000