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Lopez et al. BMC Medicine 2014, 12:200
engender a similar global response, and is it warranted?The evidence would suggest it is. While neoplasms,COPD, cardiovascular diseases and diabetes cause muchhealth loss worldwide, more of the global NCD burden(55%) arises from other NCDs. These include a diverseset of causes and conditions, but among the more im-portant are musculoskeletal disorders, especially lowback and neck pain, depression, substance use disorders,cirrhosis of the liver, chronic kidney disease, asthma,various digestive diseases including peptic ulcer, anxietydisorders, congenital anomalies and haemoglobinopa-thies. Unlike the ‘big four' NCDs, many of these condi-tions cause more health loss through chronic disabilityrather than premature death; arguably, preventingchronic disability ought to be an important goal of anyhealth system (Figure
The collection of comments in this Medicine for Glo-
bal Health forum article is a timely reminder that im-proving population health requires a focus not only onwhat is important and well-studied, but on what is im-
Figure 1 Alan Lopez is a Melbourne Laureate Professor and the
portant and hitherto largely overlooked. Levin and
Rowden-White Chair of Global Health and Burden of Disease
Tonelli point to the urgent need to improve the integra-
Measurement at The University of Melbourne. He is also Director
tion of research across the biomedical and clinical sci-
of the Global Burden of Disease Group in the Melbourne School of
ences with health systems and population-based studies
Population and Global Health.
to enhance policy and patient outcomes for chronic kid-ney disease. Peter Burney reminds us that the disease
as for leading communicable diseases. There is a very
burden from asthma is not declining very much at all,
real prospect of rates from major vascular diseases,
and that health services, particularly in poor countries,
chronic obstructive pulmonary disease (COPD) and can-
are ill-equipped to manage the case load, compounded
cers rising in men throughout the developing world dur-
by a poor supply of affordable medicines. Liver cirrhosis,
ing our lifetime as the full effects of their massive uptake
long neglected as a global health priority, is another con-
of smoking some decades ago begin to be seen This
dition where the etiology is well understood, but as
may well be compounded by the large increases in over-
Jürgen Rehm points out, policy responses have been dis-
weight and obesity that have occurred since the early
appointing, particularly in reducing alcohol consump-
1980s, firstly in developed countries, and more recently
tion, a leading risk factor for the disease. More broadly,
in many developing populations, leading to substantial
alcohol and drug use disorders are causing an increasing
increases in disease burden from diabetes Under-
share of health loss in many populations, quite apart
standably, much research and many resources worldwide
from the social pathologies associated with their use. As
have been invested in understanding the epidemiology of
Volkow and Koob argue in their article, a more effective
these conditions in order to guide treatment and pre-
response will require a serious rethink of how health
ventive programs. But, just like the policy focus of the
care services are provided, with greater emphasis on
past few decades on child survival, with comparatively
screening and improved case management.
little attention to health loss and premature death
One of the principal consequences of population
among adults, one might also ask whether too little at-
aging, namely an increase in dementia, is often at the
tention has been given in global health debates to other
forefront of policy discussions about the key implications
NCDs that, for one reason or another, might justifiably
of social, economic and health trends, but there is con-
siderable uncertainty about appropriate policy responses,
So what are these ‘forgotten NCDs' and why do they
in part because the condition is not well understood. As
matter? Just as the creation of the concept (and termin-
Ferri argues, that is changing, with recent evidence em-
ology) of ‘neglected tropical diseases (NTDs)' has led to
phasizing the importance of primary prevention to re-
much greater recognition, research support and pro-
duce this growing disease burden. The lack of visibility
grammatic response, including from institutions such as
for sickle cell disease, as Williams points out, is in part
the Gates Foundation and the World Health Organisa-
due to poor data, in part due to the fact it is concen-
tion, might a more strategic focus on neglected NCDs
trated in the world's poor, yet the condition accounts for
Lopez et al. BMC Medicine 2014, 12:200
Figure 2 (See legend on next page.)
Lopez et al. BMC Medicine 2014, 12:200
(See figure on previous page.)Figure 2 Comparison of global disease burden (in DALYs) with a focus on neglected non-communicable diseases. Pyramid: Neoplasms,COPD, cardiovascular diseases and diabetes (the ‘big four') lead to the highest proportion of disease burden among all NCDs. However, manyother NCDs lead to a comparable proportion of disease burden, yet do not receive as much attention as the ‘big four'. We have discussed sevenof these neglected NCDs (alcohol and substance abuse, liver cirrhosis, asthma, chronic kidney disease, Alzheimer's and other dementias, sickle celldisease and gout) and reviewed their disease burden. Pie chart: NCDs account for 54% of total proportion of global DALYs. Although the ‘bigfour' comprise just under half of this burden (45% of the burden of NCDs; 24.4% of the total global DALY burden) all other NCDs (i.e. theneglected NCDs) account for 55% of the burden of NCDs; 29.6% of the total global DALY burden. Data for this infographic derived from Thefigure has been prepared by BioMed Central.
over one-third of the disease burden from haemoglobi-
Competing interests
nopathies. Even gout, though a relatively minor cause of
The author declares he has no competing interests.
disease burden, is an example of a severely disablingcondition that ought, with current knowledge, be better
Sickle cell disease: a neglected non-communicable
managed and more readily preventable, as detailed in
disease of growing global importance
the article by Singh.
Thomas N Williams (Figure
Collectively, this reminds us that, unlike the acute, and
largely treatable nature of communicable diseases, NCDsare complex, diverse, and manifest their impact onpopulation health in different ways. Mitigating their im-pact will require a more strategic, comprehensive andbalanced approach to NCD research, treatment and pre-vention, beyond what has been the practice for the pasthalf century or so, giving greater emphasis to those con-ditions that are major causes of health loss, and whichhitherto have been largely ignored as global health prior-ities. So, what might public health research focus on toaccelerate the recognition of neglected NCDs as a globalhealth priority? In my view, four pillars of research andknowledge translation are critical to that endeavour:
i). rapidly reduce ignorance and uncertainty about the
true disease burden from these conditions by cost-effectively and strategically improving cause of deathand disability data collection systems;
ii). improve knowledge about the most cost-effective
strategies to reduce disease burden in different pop-ulations, and about the most appropriate and afford-able approaches to financing treatment andprevention;
iii). improve knowledge and understanding of established
interventions for controlling the impact of the moreimportant forgotten NCDs in health care debates, andpromote targeted research on promising interventionoptions where this is lacking; and
iv). raise the profile of major forgotten NCDs in national
Figure 3 Tom Williams is Professor of Haemoglobinopathy
and global health fora by developing policy relevant
Research at Imperial College London. As a clinical academic he
forecasts of likely health, economic and social costs
has been studying the epidemiology of haemoglobin disorders formore than 20 years, both in terms of the malaria protective effects
of continuing to ignore them.
of carrier forms and the global burden and consequences ofhomozygosity, particularly in relation to sickle cell disease. Based in
We should not continue to ignore or forget these NCDs.
Kenya for the last 15 years, he has recognised the growing importance
The examples reported here suggest the need for an orga-
of sickle cell disease as the country has entered its epidemiological
nized, committed and urgent response by the global health
transition. He co-chairs the Infectious Diseases Working Group of theGlobal Sickle Cell Disease Network.
community to reducing their disease burden everywhere.
Lopez et al. BMC Medicine 2014, 12:200
Few NCDs could be more neglected than sickle cell
Disease (GBD) Survey a touchstone for policy-
disease (SCD) despite the fact that, with early detec-
makers worldwide, in which causes of death were esti-
tion and an inexpensive package of basic care, the ma-
mated from vital registration, verbal autopsy (VA),
jority of those born with the condition can expect to
mortality surveillance, censuses, surveys, hospitals, and po-
lead a good quality of life into late adulthood, most pa-
lice and mortuary records. Few reliable data regarding the
tients with SCD are born in resource-limited settings
contribution of SCD to the mortality burden can be de-
(RLS) where the vast majority continue to die undiag-
rived from any of these sources, exemplified by the fact
nosed in early childhood SCD is a haemoglobin-
that before 2012, no specific questions nor any specific
opathy, which results from the pathological effects of
diagnostic codes for SCD were included in the standard
Haemoglobin S (HbS), an abnormal form of adult
WHO VA tools As a result the study grossly under-
haemoglobin (HbA) that results from a mutation (βs) in
estimated global SCD-related deaths for 2010 at 28,600
the HBB gene Most subjects with SCD are βs homo-
(16,800–40,900) a figure that should almost certainly
zygotes (sickle cell anaemia; SCA), but the condition can
be 4–6 times higher
also result from the co-inheritance of the βs mutation
Because official statistics are so poor, even basic pa-
with a range of other HBB mutations, of which the most
rameters such as the global number of affected births
common are those that result in HbC and the β-
and SCD-specific morbidity and mortality can only be
thalassaemias [Despite recent promising develop-
measured using indirect approaches. For example, we re-
ments, including its recognition by both the UN and
cently used a geostatistical model that combined data on
the WHO as a disease of major and growing import-
HbAS frequencies, overall birth rates and population
ance, for the most part SCD remains virtually invisible
densities to estimate birth rates for SCA (which accounts
on the global health agenda. In common with many
for approximately 70% of SCD) by country, concluding
neglected NCDs, to a large extent this can be attributed
that globally 312,000 (294,000 − 330,000) children were
to three interrelated issues: the fact that its greatest bur-
born with SCA in 2010, half being born in just three
den falls on the world's poorest communities, the lack of
countries: Nigeria, the Democratic Republic of Congo
reliable data and inadequate political will.
and India (Figure Similarly, by analyzing popula-
Because the carrier state for SCD (sickle cell trait;
tion data on the age-specific prevalence of SCA, an in-
HbAS) is associated with a strong survival advantage in
direct measure of the loss through death of subjects
malaria-endemic areas, the global burden of SCD is also
with this condition, we recently concluded that current
aligned to that of malaria As a consequence, the vast
under-5 mortality among children born with SCA in
majority of children with SCD are born in resource-
Africa lies between 50% and 90% As for mortality,
limited settings (RLS) (particularly sub-Saharan Africa)
the importance of SCD as a cause of global morbidity
where routine data are least reliable (Figure With few
has been consistently under-estimated through lack of
exceptions, diagnostic facilities are poor, early life
data. Nevertheless, despite this caveat the numbers re-
screening is non-existent and official statistics on health-
main impressive, with estimates from the most recent
facility usage and cause of death are sketchy within the
GBD Survey of 5,641,000 (4,244,000–7,246,000) disabil-
RLS in which the prevalence of SCD is highest. The net
ity adjusted life years lost and 2,954,000 (1,957,000–
result is illustrated by the most recent Global Burden of
4,240,000) years lived with disability .
Figure 4 Cartogram showing the estimated number of newborns with SCA by country. Cartogram showing the estimated total number ofbabies that will be born globally, by country, between 2010 and 2050. Figure adapted from Figure within reference drawn and contributedby Dr FB Piel.
Lopez et al. BMC Medicine 2014, 12:200
These global figures for morbidity and mortality should
be considered in the context of data from the North, wherein recent years, many countries have adopted universalscreening for SCD and where most now provide compre-hensive care for affected individuals. As a result, mortalityis now rare among children born with SCD in Europe, theUSA and the Caribbean where the majority of affectedchildren can expect to live a relatively normal life into their40s and 50s Providing such services is within reachin many RLS: successful pilot studies of newborn screeninghave been conducted in several African countries [and,in comparison to diseases of higher priority (such as HIV,TB and malaria), the provision of basic care in specialistclinics is not expensive If widely implemented, suchapproaches could save the lives of almost ten million chil-dren worldwide between now and 2050
So how can SCD be brought ‘out of the shadows'
of its current status as a virtually invisible NCD? Perhapsmost importantly, we need better data, without which itwill remain difficult to persuade ministries of health,policy makers, funders and the pharmaceutical industryto devote appropriate resources to the condition. Oneessential component is better data on the birth frequen-cies and survival of children with SCD at the micro-epidemiological level, potentially through investigationsusing large-scale sample sets collected for other reasons,such as national surveys of micronutrient status, HIV ormalaria prevalence. Similarly, the implementation ofearly-life screening would be made considerably simpler
Figure 5 Adeera Levin is Professor of Medicine and Head of theDivision of Nephrology, University of British Columbia, in
with the development of rapid tests that would circum-
Vancouver Canada. She is the Executive Director of the BC
vent the lack of quality-assured diagnostic laboratories
Provincial Renal Agency, and President Elect of the International
and the logistics of returning results to patients. Better
Society of Nephrology.
data will lead to better advocacy for SCD at every level:from education in schools and colleges, through togroups of affected patients, the media, celebrities, politi-
for CKD such as low birth-weight, obesity and hyperten-
cians, funders and health agencies internationally.
sion is increasing, and when superimposed on environ-mental and genetic influences may serve to amplify the
Competing interests
rising incidence of CKD over time. In addition, there are
The author declares he has no competing interests.
specific conditions (such as pregnancy, pre-eclampsia,and acute kidney injury); and specific environments
(such as tropical regions, areas of poor sanitation) that
TNW is funded by a Senior Fellowship from the Wellcome
may promote or attenuate the progression of CKD
Trust (091758). TNW thanks Dr Frederic B Piel for
The Lancet publication of the Global Burden of
contributing Figure
Disease Study 2010 (GBD 2010) serves as importantmilestone in understanding of population health and
Chronic kidney disease as a global health burden: the
disease in this century The publication highlights
need to integrate research and health policy
the value and power of data to improve our understand-
Adeera Levin (Figure and Marcello Tonelli (Figure
ing of health, its determinants, and the impact of strat-
Chronic kidney disease (CKD) is increasingly acknowl-
egies aimed at addressing specific health issues. Global
edged as a global public health problem, affecting 1 in
changes in the incidence and prevalence of key NCDs
10 adults in most jurisdictions CKD serves as a
will continue to impact the incidence of CKD. Further,
multiplier of risk in all populations and has a complex
CKD may influence global metrics of health such as years
interface with other conditions (such as diabetes and
lived with disability (YLD), given the burden faced by both
cardiovascular disease). The prevalence of risk factors
non-dialysis and dialysis CKD populations [In the
Lopez et al. BMC Medicine 2014, 12:200
Estimates of the economic burden of CKD vary de-
pending on whether dialysis and transplant therapies areincluded or excluded. Regardless, it is clear that CKD isa key driver of the high costs associated with NCDs.
One report, using provincial data in a Canadian prov-ince, described that of a cohort of patients with diabetes,cardiovascular disease and CKD, in various combina-tions: 18% of hospital costs were attributable to thosewith CKD either in isolation or combined with eitherDM or CVD. Thus of this high risk group comprising7.5% of the total cluster, an annual $ 189M was spent.
This study excluded those on dialysis or with trans-plants, and so is an underestimate of the entire burdenOthers have estimated that while the end stagerenal disease population (those on dialysis or transplant-ation) make up less than 1% of the total adult popula-tion, they consume up to 5% of national health carebudgets
The study and practice of nephrology has changed
substantially over the last 50 years. Initially nephrologywas a specialty characterized by detailed study of kidneyphysiology, but has evolved in parallel with availability ofdialysis and kidney transplantation – which are no lon-ger experimental treatments, but life-saving therapiesthat benefit hundreds of thousands of people worldwide.
Advances in diagnostics, research and more integratedapproaches to care have established CKD as a prevent-
Figure 6 Marcello Tonelli is Professor of Medicine and
able and treatable chronic disease, with multiple co-
Associate Vice President (Health Research) at the University of
morbidities that are directly and indirectly related to
Calgary in Calgary, Canada. He is Past President of the Canadian
CKD. CKD has a dramatic impact on patients and their
Society of Nephrology and Chair of the Research and Prevention
families - who must live with uncertainty, depression, and
Committee, and council member of the International Societyof Nephrology.
the symptoms of kidney disease. Since CKD is a globalproblem, different health systems, political environmentsand infrastructure have led to varied strategies and prior-
GBD 2010 report, deaths due to diabetes increased by
ities around the world. As an international nephrology
20%, and due to chronic kidney disease by 15% between
community, we recognize that sharing key discoveries,
1990 and 2010, so that both rose in the ‘league tables'
best practices and methodologies is the way forward.
of causes of death (15 to 9, and 27 to 18 respectively).
Interventions such as certain drugs, exercise, com-
This change in the relative burden of communicable
bined specialty clinics and engagement of primary care
and non-communicable diseases as drivers of mortality
and patients, have been studied and shown to improve
in most countries parallels the profound increase in the
patient outcomes. Administrative databases are used
‘lifestyle' driven risk factors CKD now ranks 39 glo-
to understand the impact of CKD on health care systems
bally as a cause of YLD, while diabetes and ischemic
and generate population-based estimates of disease burden.
heart disease rank 9 and 21 respectively. All of the condi-
An increasing number of investigator-initiated randomized
tions display regional variability, but note the YLDs due
trials have begun to address fundamental questions about
to CKD have increased by 20% since the 1990 report.
how best to care for CKD patients - how to prevent or
As infant mortality and mortality from communicable
delay kidney failure, when to commence dialysis treatment,
diseases are reduced in the developing world, the disabil-
how best to treat glomerulonephritis and to prevent rejec-
ity from NCDs will increase. Some of that disability will
tion of transplanted kidneys. As in other medical re-
be driven by CKD and all of its consequences. Identify-
searchers, kidney scientists are increasingly interested in
ing and implementing proven strategies to address risk
new translational approaches to drug development, which
factors such as hypertension, obesity, and high salt in-
may lead to the discovery of novel compounds.
take will help to reduce the burden of CKD - as demon-
A comprehensive investigative framework that includes
strated in some parts of the world such as Asia .
four pillars of research (biomedical sciences, clinical
Lopez et al. BMC Medicine 2014, 12:200
research, health systems studies and population research)
improve our ability to continue progress and sustain
is the key to improving the outcomes for patients with
focus on improving patient outcomes - across the con-
CKD. The nephrology community has built on this frame-
tinuum of kidney disease and its major risk factors.
work to integrate clinical care and health policy with theCKD research agenda. There are multiple examples of
Competing interests
teams where clinicians, investigators and administrators
The authors declare they have no competing interests.
work together to improve understanding of the burden indifferent environments. As an example, there are provin-
Gout: an Old disease with New windows of opportunities
cial, national and international specific initiatives whereby
Jasvinder A. Singh (Figure
researchers, administrators and clinicians collaboratively
Gout, a common inflammatory arthritis in adults
used data to inform decision making and track outcomes
caused by elevated levels of uric acid in the blood that
(for example, [. The CKD PC (Chronic Kidney
lead to joint inflammation and other manifestations
Disease Prognosis Consortium) has established a rich
such as kidney stones, is a major public health burden
resource, comprising over one million people with CKD in
worldwide Recognized in 2640 B.C., and later de-
various stages . The data is collated from interven-
scribed by Hippocrates as ‘the unwalkable disease',
tional trials, large cohort studies and administrative data
gout is one of the oldest known diseases. It is also a
sets, and as such covers the spectrum of CKD from high
forgotten disease. However, in terms of its impact on
risk populations to established CKD populations. Through
patients, high prevalence, well-known pathophysiology
robust analysis of data, this international group of re-
and biochemical abnormality, and availability of cheap,
searchers has established estimates for the prognosis ofmajor events, such cardiovascular disease, hospitalizations,infections, mortality and progression to end stage kidneydisease; and recently provided evidence to support a newend point in clinical trials The latter will facilitatetesting of interventions.
Awareness of CKD in the global health arena will
depend on continued efforts of the clinical and researchcommunities. The research agenda for nephrology remainsmultifaceted: the support for basic science discoveries is es-sential to uncover novel targets and mechanisms to fosterdrug or therapeutic developments. Scaling up existing ad-ministrative, research and clinical databases (some of whichhave large bio-banking platforms) will optimize the designof clinical trials, and allow clinicians to target the highestrisk individuals. New methods for setting research prior-ities, including the perspectives of administrators, healthpolicy makers, patients and their families, along with prac-ticing clinicians, remains critical. We need new studies thatinform evidence-based public policy and assess how best toallocate scarce resources to optimize health outcomes. Fi-nally, there is an increasing emphasis on evaluating the bestmethods for translation of research findings into practice,so that the science reliably benefits the patients.
CKD will continue to be a major public health prob-
lem for the foreseeable future, and the most rapid
Figure 7 Jasvinder Singh is an Associate Professor of Medicine
growth in disease burden will be in developing countries.
at the University of Alabama at Birmingham and a staff
To achieve a meaningful reduction in death and disabil-
physician at the Birmingham Veterans Affairs medical center.
ity due to CKD, the global kidney research agenda must
He is an epidemiologist and a clinician with 14 years of experiencein treating rheumatic conditions. His research focus is health services
encompass and integrate basic, clinical, health outcome,
and outcomes research in patients with arthritis with a focus on
and population health perspectives. The international
gout, osteoarthritis and arthroplasty. Another area of interest is
nephrology community is committed to this engagement
systematic reviews and meta-analyses, with a focus on Network
of patients, healthcare administrators and policymakers
Meta-analyses. He is the Director of the UAB Cochrane Musculoskeletal
in the research agenda. The recognition of CKD as
Group Satellite Center and serves on several national andInternational organizations.
important in the global health and NCD agendas will
Lopez et al. BMC Medicine 2014, 12:200
affordable treatments, it's clearly a missed opportunity
The rates of joint fluid aspirate-proven diagnosis of gout
in medicine.
are low. Given the common involvement of great toe
In the course of several diseases such as diabetes, can-
and other lower extremity joints in two other common
cer, rheumatoid arthritis and others, there is a single
conditions, osteoarthritis and pseudogout, a presumptive
window of opportunity, where interventions in early dis-
diagnosis of gout based on a history of big toe pain and
ease can prevent future complications. In comparison,
a borderline high or higher than normal range serum
gout has several windows of opportunities throughout
urate level is problematic (Figure Documentation of
the disease course and amongst various aspects of
additional clinical features of acute synovitis, radio-
the disease. The incidence and prevalence of gout seems
graphic signs of overhanging margin and punched-out
to be increasing according to several epidemiological
erosions typical of gout, and close attention to looking
studies. The Rochester Epidemiology project (REP)
for features of other differential diagnoses (osteoarthritis,
showed a similar increase in the incidence of gout from
pseudogout and rheumatoid arthritis), will often help
0.045% in 1977–1978 to 0.061% in 1995–1996 . A
in a correct diagnosis of gout. The 1977 American
study in a health maintenance organization showed an
Rheumatism Association (ARA) preliminary criteria for
almost doubling of prevalence of gout and/or hyperuri-
classification of acute gouty arthritis are also commonly
cemia from 2% in 1990 to 4% in 1999 A study based
used for a clinical diagnosis of gout, but are inadequate
on National Health and Nutrition Survey (NHANES) also
for in-office diagnosis in about 21% of cases . At-
found that the prevalence of self-reported physician-
tempts should always be made to aspirate joint/bursa/
diagnosis of gout increased from 2.7% in 1988–1994 to
tophus and confirm the diagnosis, since documentation of
3.9% in 2007–08 ]. Many of these opportunities may be
urate crystals in synovial fluid confirms gout as a single test
missed, leading to an increased burden of gout in the face
and the treatment for gout is often life-long.
of neglected prospects for diagnosis and treatment.
Third is the challenge of optimal control of serum
First, physicians and patients need to update their
urate. Urate-lowering therapy (ULT), including allopur-
knowledge regarding the dietary and lifestyle risk factors
inol and uricosurics are generic, affordable and the most
for gout in order to take advantage of these windows of
commonly used drugs; febuxostat, a new ULT, is also
opportunities. New information from well-designed epi-
available but is more expensive. ULT helps to lower
demiological studies is available, which update our
serum urate levels, a central biochemical abnormality in
knowledge of the disease (based on clinical anecdotes)
gout. Current guidelines recommend achieving target
and confirm or refute previous prevalent beliefs about
serum urate of <6 mg/dl which is achieved by at
gout. Higher intake of meats, seafood, alcohol (in par-
most 33% of patients This is a meaningful dis-
ticular beer) and sugar-sweetened soft drinks (including
ease target since it is associated with improved clinical
fruit juices and sodas) increase the risk of gout, while
outcomes such as reduction in gout flares, regression of
low fat dairy products, Vitamin C supplements and cof-
tophi and lower health care costs (Figure
fee decrease the risk of gout (Figure Importantly,
Achievement of this serum urate target frequently re-
purine-rich vegetables and nuts do not increase the risk
quires titration of allopurinol dose, sometimes up to 900
of incident gout A higher intake of purine-rich
mg/day rather than a monotonic 300 mg/day dose
foods from animal sources (meats etc.) and alcohol in-
Physicians aiming to help gout patients avoid flares
creases the risk of gout flares Since environmen-
and improve function to reap the full benefits of treat-
tal factors play a big role in the risk of gout as well as
ment need to monitor serum urate after starting ULT
risk of gout flares, they should be one of the main
and follow a treat-to-target approach. We believe that it
foci of gout management. Our recent work with pa-
is possible to achieve disease remission in many gout pa-
tients shows that they are interested in discussing
tients with this approach. This is a paradigm shift in
these options with their providers as part of their gout
gout treatment that is likely to improve patient out-
management Physicians can counsel patients
comes. A patient-physician collaborative approach is es-
during their regular follow-up regarding strategies to
sential for this to succeed.
prevent gout and in those with gout, ways to decrease
We have summarized briefly a few opportunities for
the risk and suffering from gout flares. Therefore, this
improving care and outcomes of gout, for which there
is one key area of opportunity for both physicians and
are several additional opportunities for interventions not
mentioned here. We are at the brink of new treatment
Second is the challenge of correctly diagnosing gout.
options for gout, a better understanding of its impact on
Gout manifests as intermittent monarticular acute arth-
cardiovascular and renal disease, and better management
ritis in the early years/phase of the disease and as
with existing pharmacological and non-pharmacological
chronic polyarthritis with intermittent flares in the later
treatment approaches. This is an exciting era in which
years. Tophi and renal stones may accompany arthritis.
we know ever more about this ancient disease.
Lopez et al. BMC Medicine 2014, 12:200
Figure 8 Epidemiology, diagnosis and optimal management of gout.
Competing interestsJAS has received research grants from Takeda and Savientand consultant fees from Savient, Takeda, Regeneron andAllergan. JAS is a member of the executive of OMERACT,an organization that develops outcome measures inrheumatology and receives arms-length funding from 36companies; a member of the American College of Rheu-matology's Guidelines Subcommittee of the Quality ofCare Committee; and a member of the Veterans AffairsRheumatology Field Advisory Committee.
AcknowledgementsJAS is supported by grants from the Agency for HealthQuality and Research Center for Education and Researchon Therapeutics (AHRQ CERTs) U19 HS021110, NationalInstitute of Arthritis, Musculoskeletal and Skin Diseases(NIAMS) P50 AR060772 and U34 AR062891, NationalInstitute of Aging (NIA) U01 AG018947, National CancerInstitute (NCI) U10 CA149950, and research contract CE-1304-6631 from the Patient Centered Outcomes ResearchInstitute (PCORI). JAS is also supported by the re-sources and the use of facilities at the VA MedicalCenter at Birmingham, Alabama, USA. The fundingsources (National Institutes of Health and others) had norole in study conception, protocol development, data ana-
Figure 9 Peter Burney is Professor of Respiratory Epidemiologyand Public Health at the National Heart and Lung Institute,
lyses, manuscript preparation or decision to submit.
Imperial College London. Until 2006 he was Chair of Public Health andPrimary Care at King's College London. In the late 1980s he started the
Asthma: a challenge for health care providers
European Community Respiratory Health Survey to study asthma and
Peter G. J. Burney (Figure
allergies in adults, mostly in Western Europe. Currently he co-ordinates
Asthma is generally defined as a reversible obstruction
the Burden of Obstructive Lung Disease Study, a study of chronicobstructive lung disease mostly in low and middle income countries.
of the airway and is one of the most common chronic
Lopez et al. BMC Medicine 2014, 12:200
conditions. Since the 1980s the term has come increas-
marked decline in lung function This will lead to
ingly to signify any wheezy illness that responds to bron-
an increasing problem for an ageing population what-
chodilators. Compared with other chronic lung diseases
ever changes in prevalence occur. The burden associated
it starts much younger and because the mortality is rela-
with asthma is therefore likely to increase both because
tively low and the disease tends to persist, it maintains a
of continuing urbanisation in the poorer countries and
high prevalence in the population.
because of the ageing of the population everywhere.
Asthma is generally divided into allergic and non-
Currently there is wide variation in the relative impact
allergic. The relation of asthma to allergic sensitisation is
of asthma on mortality. Although asthma ranks as only
complicated. Both sensitisation and atopic diseases such
the 42nd most common cause of death globally, it is
as asthma run in families, but they are not inherited in
much more highly ranked in Oceania (13th), South East
the same way In childhood, asthma associated
Asia (25th), South Asia (26th) and North Africa and the
with allergies is more persistent and tends to be more
Middle East (30th) than in Southern and Andean (65th
severe. In adulthood ‘non-allergic' asthma tends to be
and 62nd) Latin America and Western Europe (60th).
more severe. In childhood allergies are less common in
Because asthma often has an early onset and is persist-
low income countries, as are the atopic conditions asso-
ent throughout life, it is a relatively important cause of
ciated with allergies, but non-allergic wheeze is equally
disability adjusted life years lost (DALYs), ranking 28th
common in countries at all economic levels The
globally among the causes of DALYs but 8th in Oceania,
prevalence of allergic sensitisation has been increasing
15th in Australasia and Tropical Latin America, 18th is
over the long term though more recent changes in
South East Asia and 19th in the Caribbean
the prevalence of atopic conditions such as asthma have
The chronic nature of asthma requires continuous
been more variable among children
care and reliable access to affordable medications. These
The International Study of Asthma and Allergies in
conditions have been set out by the Global Initiative for
Childhood (ISAAC) Study was the largest global survey
Asthma (GINA) together with the need to prevent
of the prevalence of asthma, rhinitis and eczema involv-
exacerbations with the use, in the first instance, of in-
ing almost 2,000,000 children in 105 countries. This
haled corticosteroids. However the costs and availability
study has shown very wide variations in the prevalence
of inhaled steroids are very variable and there is a ten-
of wheezy illness, with very high rates in the English
dency for these to cost more in low income countries
speaking countries and Latin America and wide varia-
This leads to poor management and reliance on
tions even across single continents such as Europe,
emergency rooms to provide care, a wasteful and less ef-
where rates fall from high levels in the northwest to low
fective method of managing the condition. In a survey of
levels in the southeast The prevalence of more se-
treatment failures seen in emergency rooms in 11 coun-
vere disease has a different distribution, however, with a
tries, patients with inadequate insurance and those with-
far higher proportion of cases being recorded as severe
out a consistent source of continuing medical care were
in sub-Saharan Africa in particular
less likely to be on the recommended dose of inhaled
Information on adults is more sparse and comes from
steroids. In addition, those without adequate steroid use
the European Community Respiratory Health Survey
were more likely to have lost work because of asthma in
(ECRHS) and the World Health Survey Although
the recent past demonstrating the high cost to pa-
mean prevalence is least common in middle-income
tients and their families of inappropriate care.
countries, the maximum prevalence recorded in the poor-
Asthma is a common condition that causes considerable
est countries is below the maximum prevalence in middle
morbidity and with increasing age leads to a disease that is
or high income countries. Sampling decisions need to in-
more difficult to manage, along with increasing mortality.
form the interpretation of all these studies. For instance,
Although it is mostly not difficult to manage, along with
in low income countries there has been a consistent find-
other chronic conditions it requires continuous care,
ing that asthma is less common in rural areas ] and
which traditional health services are not designed to pro-
over sampling of urban populations may therefore inflate
vide. Currently the problem of inadequate health services
overall estimates in low income countries.
is compounded by a poor supply of over-priced medica-
Asthma is not a common cause of death and age-
tions. These problems are shared by other chronic condi-
standardised death rates fell by 42% between 1990 and
tions and have common solutions including the provision
2010 from 9.0 to 5.2 per 100,000. However, the global
of continuous long-term care and reliable access to afford-
number of deaths fell only 9% from 380,000 to 346,000
able, high-quality medication.
between 1990 and 2010 The slower rate of declinein total deaths represents the aging of the population.
Competing interests
Mortality from asthma increases markedly with age
PGJB has acted as a Consultant to Novartis through
and with age some patients with asthma experience a
Lopez et al. BMC Medicine 2014, 12:200
Liver cirrhosis – time for addressing a neglected
Global death rates due to liver cirrhosis seem to have
non-communicable chronic disease
been quite stable over the years: the World Health
Jürgen Rehm (Figure
Organization (WHO) estimated and predicted 14.5 deaths
Liver cirrhosis is an abnormal condition with irrevers-
per 100,000 for the years 2000 and 2030, respectively, with
ible scarring as a result of continuous and long-term
almost no variation for years in between However,
liver damage, which is primarily caused by excessive al-
when standardized rates are considered, liver cirrhosis
cohol consumption, hepatitis, and non-alcoholic steato-
deaths are predicted to decrease.
hepatitis. It is among the top 15 causes of death globally
There are several factors that may become important
and, in 2012, was estimated to have caused more than
to explain trends for liver cirrhosis. A downward trend
1,000,000 deaths and more than 36,000,000 years of lives
in high income countries may be predicted to be linked
lost to either premature death or disability.
to improved clinical practices leading to lower case fatal-ity rates although there is not much evidence onthis, and, to give just one example, historically, case fa-tality rates have not shown any improvement over thetime period between 1968 and 1999 in England Anupward trend may be linked to increases in alcohol con-sumption in low- and mid-income countries as they in-crease their economic wealth In terms of burden ofdisease, most DALYs were derived from years of life lostto mortality, that is, due to the high case fatality. However,as indicated above, this may constitute an underestimatefor high-income countries due to the lower case fatalityand thus higher duration of living with disability.
While the overall prevalence of liver cirrhosis mortal-
ity and burden of disease seems stable, there are hugevariations by gender, age and regions [and they seemto be caused by preventable risk factors. Men have consid-erably higher rates of liver cirrhosis morality and burden ofdisease, globally more than twofold the rates of women,and highest in the men between 50 and 69 years of age.
The only exception for the higher prevalence of liver cir-rhosis mortality and burden is the Eastern Mediterraneanregion, where women have slightly higher rates; this regionalso has by far the lowest alcohol consumption whichis the main risk factor for liver cirrhosis.
Figure gives an overview of the burden of disease of
liver cirrhosis for the year 2012 in DALYs by WHO region,and the role of alcohol in causing this disease (data basedon . As indicated above, alcohol consumption isglobally the most important risk factor for liver cirrhosis,
Figure 10 Jürgen Rehm, Ph.D. has been appointed the
responsible for about half of the global burden (50%; men:
Inaugural Chair for Addiction Policy at the Dalla Lana School of
53%; women: 44%; ; other main global risk factors are
Public Health of the University of Toronto. In addition he holds
hepatitis B and C, and obesity ,]. Europe, especially
positions at the Centre for Addiction and Mental Health (Toronto,
the Eastern European region, has the highest rate of liver
Canada) as Director of the Social and Epidemiological ResearchDepartment and Head of the PAHO WHO Collaborating Centre, and
cirrhosis, with alcohol consumption a large factor (63%).
at the Institute for Clinical Psychology and Psychotherapy of the
For low- and mid-income countries, hepatitis-induced
Technical University Dresden (Germany). Dr. Rehm has published more
liver cirrhosis is relatively more important, with the rela-
than 600 peer-reviewed publications in addiction research, comprising
tive impact differential between high income and other
studies in epidemiology, economics and clinical research, the latter
countries being largest for hepatitis B [.
especially in the area of treatment evaluation. He is listed among theISI/Thompson Reuters most highly cited in the fields of social research
The role of alcohol consumption in causing and wors-
and epidemiology and has been awarded the Jellinek Award, the most
ening the course of liver cirrhosis has been evident on
prestigious award in alcohol research. He has served as public health
the individual level and on the aggregate level in
consultant to many countries, and is currently member of the WHO
comparisons between countries ], or in analyses over
Expert Advisory Panel on Drug Dependence and Alcohol Problems.
time It is important to understand that alcohol
Lopez et al. BMC Medicine 2014, 12:200
Figure 11 Disability adjusted life years due to liver cirrhosis per 100,000 population in WHO regions in 2012. Afr: African region. Amr:Americas. Emr: Eastern Mediterranean region. Eur: Europe. Sear: South East Asian Region (including India). Wpr: Western Pacific Region.
consumption increases the risk of mortality for all kinds
of liver cirrhosis, independent of the original aetiology
I would like to thank Drs. Gretchen Stevens, Michael
(3), and thus abstinence is the major goal in most guide-
Livingstone and Robin Room, who provided important
lines for treatment of liver cirrhosis.
information for this article.
Intervention studies show that a reduction of alcohol
consumption via policy interventions resulted in a
Substance use disorders: implications for global health
marked reduction of liver cirrhosis (for example in
Nora D Volkow (Figure and George Koob (Figure
Russia Although liver cirrhosis is a chronic dis-
Substance use disorders (SUD) associated with legal
ease, interventions have immediate effects, as not only
substances are two of the three leading contributing fac-
shown by the Russian experiences cited above, but also
tors for global burden of disease and injury (DALYs for
for instance by the impact of the German seizures of al-
tobacco: 6.3%; for alcohol: 5.5%) and those associated
cohol on French mortality rates during World War II, or
with illicit substances are within the top twenty factors
the impact of prohibition in the US It may
(DALYs 0.8%) ]. The past 20 years has seen an in-
take up to 20 years, however, before all of the effects of
crease in the contribution of SUD to the global burden
interventions can be seen
of disease, mostly from alcohol (32%) and illicit drugs
A sizable portion of liver cirrhosis mortality could be
(57%) . Moreover, the global burden of disease attribut-
reduced in the first year after implementing effective in-
able to SUD is likely to be underestimated particularly for
terventions to reduce alcohol, such as higher taxation,
illicit substances due to incomplete epidemiological data
decreased availability, advertisement and marketing bans
on estimates of impactful and preventable outcomes (i.e.
or brief interventions and treatment especially
injuries, violence and mental health problems) []. Thus,
among heavy drinkers ]. The effect is more pro-
SUV prevention and treatment would have a major impact
nounced for heavy drinkers because the risk curve for
in improving public health globally.
mortality is exponential; that is, relatively more mortality
The recent endorsement by the United Nations Office
can be avoided for the same amount of reduction in
on Drugs and Crime (UNODC) of addiction as a brain
average drinking for heavy drinkers compared to light or
disease and the recommendation that it should be
moderate drinkers Such interventions would not
treated as a medical and public health issue rather than
only reduce liver cirrhosis rates but also other causes of
a criminal justice and or moral issue highlights the role
mortality such as other non-communicable diseases
that the healthcare system can play in the prevention
(cancers, hypertensive heart disease, stroke, pancreatitis)
and treatment of SUD The conceptualization of ad-
or injuries Given this situation, and given
diction as a brain disease reflects in part findings from
the fact that there are proven effective interventions to
brain imaging studies and preclinical research that have
reduce alcohol consumption, we see no reason why glo-
identified the brain circuits that are disrupted by drugs
bal liver cirrhosis rates should continue to be as high as
(legal and illegal) and how their disruption impairs the
they are now.
addicted individual's ability to control his/her behaviourMoreover, excessive drug and alcohol use in adoles-
Competing interests
cence impairs executive function and increases the vul-
The author declares he has no competing interests.
nerability to SUDs in adulthood. Clinical studies have
Lopez et al. BMC Medicine 2014, 12:200
Figure 12 Nora D Volkow is Director of the National Institute
Figure 13 George F. Koob was recently appointed Director of
on Drug Abuse; a position she had held since 2003. Her
the National Institute on Alcohol Abuse and Alcoholism after
research transformed the drug addiction field by providing the first
30 years at The Scripps Research Institute in La Jolla California.
evidence for specific molecular (loss of striatal D2 receptors) and
His research has focused on the dysregulation of the brain arousal
functional (impaired frontal control circuitry) changes in brains of
and stress systems that drive compulsive drug and alcohol seeking.
addicted individuals that link to compulsivity and loss of control. She
He has made significant contributions to our understanding of the
has also made ground-breaking discoveries in the neurobiology of
neurocircuitry of negative emotional states and their role
ADHD and obesity.
in pathophysiology.
also shown that SUD can be prevented and treated, and
mental illnesses, since they are frequently co-morbid with
like other chronic diseases requires continuity of care
SUD, and inappropriate management of either condition
Because all countries have health care infrastruc-
exacerbates the other. Similarly, integrated care is funda-
ture, it is recommended that these healthcare systems
mental for the treatment of infectious diseases such as
integrate treatment of SUD within the system norms.
HIV and HCV for which substance abusers are at higher
Drug associated health consequences are still some of
risk and for which compliance with medical treatment of
the main preventable causes of disability and the health-
the infectious disease requires parallel treatment of the
care system can play a crucial role in their prevention
SUD. In addition, SUD is the main underlying cause of ve-
and treatment. This recommendation provides a plat-
hicle accidents. Therefore, integrated care will also facilitate
form that is relevant and available to countries with dif-
addressing this factor, for if untreated the alcoholic or drug
ferent levels of economic development.
abuser will continue to contribute to repeated incidents.
Health care systems can participate at all levels in the se-
Moreover, in these times of increasing health care costs
verity range of SUD, starting from its prevention to serving
and burden, treating SUD's would translate into significant
as a referral for specialized care for the most severe cases.
savings in the need to treat the secondary health costs
Health care systems can also maximize the opportunity
to integrate the care for the health problems associated
The challenges in implementing healthcare involve-
with SUD. Of particular importance is the management of
ment in SUD management are complex and will vary
Lopez et al. BMC Medicine 2014, 12:200
among countries on the basis of their economic re-
of 65. Older people are likely to have multiple health
sources, cultural norms, drug availability and policies to-
conditions. Dementia however, has a disproportionate
wards criminalization and legalization of drugs. This is
impact on independent living, being a major cause of
further compounded by rapid changes in the use of
disability and dependence among older people.
drugs across the world, such as movements towards
With the rapid ageing of the population worldwide, the
legalization of marijuana, recent access to electronic
number of people with dementia is predicted to rise. It
drug delivery devices, rapid dissemination of new syn-
is estimated that in 2010 there were 35.6 million people
thetic drugs and the increased abuse of prescription
with dementia, and predictions based on population age-
medications. The opportunities that the healthcare sys-
ing show that this figure is likely to double every 20
tem offers towards the control of SUD highlight the ur-
years, reaching 115.4 million by 2050 Most people
gent need for educating health care providers in the
with dementia already live in low- and middle-income
screening and management of SUD and the need to allo-
countries (LMIC) and these same estimates predict that
cate the resources necessary for its implementation.
by 2050 more than 70% of people with dementia will beliving in these countries
Competing interests
It has been estimated that the total worldwide cost of
The authors declare they have no competing interests.
dementia was US$604 billion in 2010 ]. While mostof these costs are concentrated in high income coun-
Placing dementia in the NCDs prevention strategies
tries, where the costs are divided roughly equally be-
Cleusa P. Ferri (Figure
tween formal (hospital and social) and informal (family)
Dementia is a syndrome that usually involves with loss
care settings, in low- and middle-income countries, in-
of memory, reasoning, and other cognitive functions
formal care costs account for the vast majority of total
progressively impairing an individual's everyday func-
costs with the burden concentrated on families and
tioning. The main risk factor for dementia is age, with
informal carers. Formal costs are likely to increase in
prevalence roughly doubling every 5 years over the age
these countries, not only due to the increasing numbersof people with dementia in the future, but also becauseof a shift in the balance between informal and formalcare as the health care sectors develops in LMIC.
Future estimates are mostly based on population age-
ing and include the assumption that age-specific preva-lence will be stable over time. However, some recentstudies have suggested that over the past 20 to 30 yearsthere has been a decline in the predicted burden of de-mentia in high-income countries [In the UK, forexample, a recent study indicates a reduction in de-mentia prevalence of around 20% over a 20-year period(from 1989–1994 to 2008–11). These reductions suggestthat predicted dementia cases were perhaps avoided ordelayed by changes in the risk factors for dementia atearlier ages, suggesting that these risks are modifiableand dementia, to some extent, can be prevented or, atleast, the risk reduced at particular ages.
Figure 14 Cleusa P. Ferri is an Affiliated Professor at the
One possible explanation for the reduction in demen-
Universidade Federal de Sao Paulo in the post-graduation
tia is the change in cardiovascular diseases and risk fac-
program of the Psychobiology Department, supported by
tors. There is growing evidence supporting a strong
Associação Fundo de Incentivo a Pesquisa (AFIP), and a SeniorEpidemiologist at the Institute of Education and Health Sciences
and likely causal association between cardiovascular
at the Hospital Alemao Oswaldo Cruz, Brazil. She worked as an
disease (CVD) and its risk factors, and dementia
international specialist on dementia for the Global Burden of Disease
Therefore, the changes seen regarding the reduction in
2010 Project. In the same capacity, she was also involved with the
dementia prevalence are likely partially due to improve-
MHGap project with the WHO. For 10 years Dr Ferri worked at the
ments in service provision and disease management of
Institute of Psychiatry, King's College London. During this period,apart from her teaching and other research activities, she worked
CVD, and also to changes in behaviour, with around
with the 10/66 Dementia Research Group, studying the epidemiology
half of the reduction in morbidity and mortality thought
of dementia in low- and middle-income countries. She returned to
to be accounted for by primary prevention. However,
Brazil, her home country, in 2013 and is now focusing her work on the
current models to estimate the impact of preventive strat-
epidemiology of ageing and dementia in Brazil and Latin America.
egies on future vascular diseases do not consider the
Lopez et al. BMC Medicine 2014, 12:200
impact on dementia. Some non-communicable diseases
Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada. 6Medicine Service and
(NCDs), such as cardiovascular diseases, are risk factors
Center for Surgical Medical Acute care Research and Transitions, VA MedicalCenter, 510, 20th street South, Birmingham, AL FOT 805B, USA. 7Department
for dementia and many risk and protective factors for de-
of Medicine at School of Medicine, and Division of Epidemiology at School
mentia are the same as those for other NCDs How-
of Public Health, University of Alabama, 1720 Second Ave. South,
ever, most countries' policies and prevention strategies for
Birmingham, AL 35294-0022, USA. 8Department of Orthopedic Surgery, MayoClinic College of Medicine, 200 1st St SW, Rochester, MN 55905, USA.
NCDs do not include the prevention, or reduction of risk,
9National Heart and Lung Institute, Imperial College, London, UK. 10Centre for
of dementia, despite some recent initiatives ].
Addiction and Mental Health, Toronto, Canada. 11Clinical Psychology and
In low-, middle- and high-income countries, dementia
Psychotherapy, Technical Universität Dresden, Dresden, Germany. 12AddictionPolicy, Dalla Lana School of Public Health, University of Toronto (UofT),
can be seen as part of normal ageing. Although demen-
Toronto, Canada. 13Department of Psychiatry, Faculty of Medicine, UofT,
tia is indeed common in the oldest age groups, it is not
Toronto, Canada. 14Institute of Medical Science, UofT, Toronto, Canada.
15
an inevitable consequence of long lifespans. Increasing
National Institute on Drug Abuse, National Institutes of Health, Rockville,
MD, USA. 16National Institute on Alcohol Abuse and Alcoholism, National
awareness of dementia in society as whole, from patients
Institutes of Health, Bethesda, MD 20892-9304, USA. 17Institute of Education
to policy/decision makers, can contribute not only to de-
and Health Sciences, Hospital Alemao Oswaldo Cruz, Rua João Julião,
creasing stigma and increasing community solidarity,
245 – Bloco D CEP 01323-903, São Paulo, SP, Brazil. 18Department ofPsychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo,
but also to improving the capacity of existing services
Rua Botucatu, 862- 1o andar, São Paulo, CEP 04023-062, Brazil.
with evidence based approaches that can meet the needsof older people and those with dementia. It is important
Received: 3 October 2014 Accepted: 3 October 2014
to note that awareness campaigns need to be carried outwith great care in order to avoid raising expectationsthat cannot be met, and avoid leading to unintended
consequences, such as increased stigma and fear, through
Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, Naghavi M,Salomon JA, Shibuya K, Vos T, Wikler D, Lopez AD: GBD 2010: design,
use of dramatic imagery and language.
definitions, and metrics. Lancet 2012, 380:2063–2066.
Dementia costs to individuals, families and society as a
Peto R, Lopez AD: The future worldwide health effects of current
whole will grow as the number of people with dementia
smoking patterns. In Tobacco and Public Health: Science and Policy. Editedby Boyle P, Gray N, Henningfield J, Safrin J, Zatonski W. Oxford: Oxford
increases, and this will have an even greater impact on
University Press; 2004:281–286.
LMIC, which have fewer resources and where popula-
Murray CJ, Lopez AD: Measuring the global burden of disease. N Engl J
tion ageing is happening faster than in rich countries.
Med 2013, 369:448–457.
Grosse SD OI, Atrash HK, Amendah D, Piel FB, Williams TN: Sickle cell
Dementia should be on the public health agenda of each
disease in Africa: a neglected cause of early child mortality. Am J Prev
country, with careful consideration given to each coun-
Med 2011, 41(6 Suppl 4):S398–405
try's demographic and sociocultural context, including
Rees DC, Williams TN, Gladwin MT: Sickle-cell disease. Lancet 2010,376:2018–2031.
their own stage of the unfolding demographic and health
United Nations press office. Press conference on raising awareness of
transitions. The impact of change to risk factor profiles
sickle-cell anaemia:
in countries is difficult to predict. However, models look-
ing at the relative impact of primary prevention in com-
World Health Organization Regional Office for Africa: Sickle-cell disease:a strategy for the WHO African Region. Report of the Regional Director.
parison to approaches focused more on secondary
AFR/RC60/8. 2010.
prevention suggest that up-stream primary prevention is
Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Williams TN,
likely to be the cheapest and most efficient way to
Weatherall DJ, Hay SI: Global distribution of the sickle cell gene andgeographical confirmation of the malaria hypothesis. Nat Commun 2010,
decrease the burden of dementia for future generations
reducing the need for costly screening and
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Amann M,
treatment regimens for established disease. It is important
Anderson HR, Andrews KG, Aryee M, Atkinson C, Bacchus LJ, Bahalim AN,Balakrishnan K, Balmes J, Barker-Collo S, Baxter A, Bell ML, Blore JD, Blyth F,
to strengthen the evidence on the effectiveness of demen-
Bonner C, Borges G, Bourne R, Boussinesq M, Brauer M, Brooks P,
tia prevention programmes, including their timescales,
Bruce NG, Brunekreef B, Bryan-Hancock C, Bucello C, et al: A comparative
and also to ensure that dementia takes its place in NCD
risk assessment of burden of disease and injury attributable to 67 riskfactors and risk factor clusters in 21 regions, 1990–2010: a systematic
policies and prevention strategies.
analysis for the Global Burden of Disease Study 2010. Lancet 2012,380:2224–2260.
Conflict of interest
Ndila C, Bauni E, Nyirongo V, Mochamah G, Makazi A, Kosgei P, Nyutu G,Macharia A, Kapesa S, Byass P, Williams TN: Verbal autopsy as a tool for
Cleusa Ferri has been named as a local principal investi-
identifying children dying of sickle cell disease: a validation study
gator in an upcoming trial sponsored by Merck.
conducted in Kilifi district, Kenya. BMC Med 2014, 12:65.
Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN: Global burden of
sickle cell anaemia in children under five, 2010–2050: modelling based
1School of Population and Global Health, The University of Melbourne,
on demographics, excess mortality, and interventions. Plos Med 2013,
Building 379, 207 Bouverie St, Carlton, Melbourne, VIC 3053, Australia.
2Department of Medicine, Imperial College, St Mary's Hospital, London
Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Dewi M, Temperley
W21NY, UK. 3KEMRI/Wellcome Trust Research Programme, PO Box 230, Kilifi,
WH, Williams TN, Weatherall DJ, Hay SI: Global epidemiology of sickle
Kenya. 4University of British Columbia, St Paul's Hospital, 1081 Burrard Street
haemoglobin in neonates: a contemporary geostatistical model-based
Rm 6010 A, Vancouver, BC V6Z1Y8, Canada. 57th Floor, TRW Building, 3280
map and population estimates. Lancet 2013, 381(9861):142–151
Lopez et al. BMC Medicine 2014, 12:200
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M,
Arromdee E, Michet CJ, Crowson CS, O'Fal on WM, Gabriel SE: Epidemiology of
Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I,
gout: is the incidence rising? J Rheumatol 2002, 29:2403–2406.
Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM,
Wallace KL, Riedel AA, Joseph-Ridge N, Wortmann R: Increasing prevalence
Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Col o S, Barrero LH,
of gout and hyperuricemia over 10 years among older adults in a
Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, et al: Disability-
managed care population. J Rheumatol 2004, 31:1582–1587.
adjusted life years (DALYs) for 291 diseases and injuries in 21 regions,
Zhu Y, Pandya BJ, Choi HK: Prevalence of gout and hyperuricemia in the
1990–2010: a systematic analysis for the Global Burden of Disease
US general population: the National Health and Nutrition Examination
Study 2010. Lancet 2012, 380:2197–2223.
Survey 2007–2008. Arthritis Rheum 2011, 63:3136–3141.
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K,
Choi HK: A prescription for lifestyle change in patients with
Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn
hyperuricemia and gout. Curr Opin Rheumatol 2010, 22:165–172.
SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson
Zhang Y, Chen C, Choi H, Chaisson C, Hunter D, Niu J, Neogi T: Purine-rich
C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez
foods intake and recurrent gout attacks. Ann Rheum Dis 2012, 71:1448–1453.
MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, et al: Years lived with dis-
Zhang Y, Woods R, Chaisson CE, Neogi T, Niu J, McAlindon TE, Hunter D:
ability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010:
Alcohol consumption as a trigger of recurrent gout attacks. Am J Med
a systematic analysis for the Global Burden of Disease Study 2010.
2006, 119:800. e813-808.
Lancet 2012, 380:2163–2196.
Singh JA: Research priorities in gout: the patient perspective. J Rheumatol
Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J, Newell H, Smalling B,
2014, 41:615–616.
Amos R, Stephens A, Rogers D, Kirkham F: Clinical outcomes in children
Singh JA: The Impact of Gout on Patient's Lives and Differences by
with sickle cell disease living in England: a neonatal cohort in East
Gender and Race: A Patient Perspective. Arthritis Res Ther 2014,
London. Haematologica 2007, 92:905–912.
Malik A, Schumacher HR, Dinnella JE, Clayburne GM: Clinical diagnostic
Quinn CT, Rogers ZR, McCavit TL, Buchanan GR: Improved survival of
criteria for gout: comparison with the gold standard of synovial fluid
children and adolescents with sickle cell disease. Blood 2010,
crystal analysis. J Clin Rheumatol 2009, 15:22–24.
Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Pil inger MH,
Wierenga KJ, Hambleton IR, Lewis NA: Survival estimates for patients with
Merill J, Lee S, Prakash S, Kaldas M, Gogia M, Perez-Ruiz F, Taylor W, Liote F, Choi
homozygous sickle-cell disease in Jamaica: a clinic-based population
H, Singh JA, Dalbeth N, Kaplan S, Niyyar V, Jones D, Yarows SA, Roessler B, Kerr
study. Lancet 2001, 357:680–683.
G, King C, Levy G, Furst DE, Edwards NL, Mandell B, Schumacher HR, et al: 2012
Ware RE: Is sickle cell anemia a neglected tropical disease? PLoS Negl Trop
American College of Rheumatology guidelines for management of gout.
Dis 2013, 7:e2120.
Part 1: systematic nonpharmacologic and pharmacologic therapeutic
Amendah DD, Mukamah G, Komba A, Ndila C, Williams TN: Routine
approaches to hyperuricemia. Arthritis Care Res 2012, 64:1431–1446.
paediatric sickle cell disease (SCD) outpatient care in a rural Kenyan
Dalbeth N, House ME, Horne A, Petrie KJ, McQueen FM, Taylor WJ:
hospital: utilization and costs. PLoS One 2013, 8:e61130.
Prescription and dosing of urate-lowering therapy, rather than patient
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F,
behaviours, are the key modifiable factors associated with targeting
Levey AS: Prevalence of chronic kidney disease in the United States.
serum urate in gout. BMC Musculoskelet Disord 2012, 13:174.
JAMA 2007, 298:2038–2047.
Sarawate CA, Patel PA, Schumacher HR, Yang W, Brewer KK, Bakst AW:
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY,
Serum urate levels and gout flares: analysis from managed care data.
Yang CW: Chronic kidney disease: global dimension and perspectives.
J Clin Rheumatol 2006, 12:61–65.
Lancet 2013, 382:260–272.
Singh JA, Hodges JS, Asch SM: Opportunities for improving medication
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J,
use and monitoring in gout. Ann Rheum Dis 2009, 68:1265–1270.
Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM,
Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C: Clinical
Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML,
efficacy and safety of successful longterm urate lowering with
Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth
febuxostat or allopurinol in subjects with gout. J Rheumatol 2009,
F, Bolliger I, Boufous S, Bucello C, Burch M, et al: Global and regional mor-
tality from 235 causes of death for 20 age groups in 1990 and 2010: a
Halpern R, Fuldeore MJ, Mody RR, Patel PA, Mikuls TR: The effect of serum
systematic analysis for the Global Burden of Disease Study 2010. Lancet
urate on gout flares and their associated costs: an administrative claims
analysis. J Clin Rheumatol 2009, 15:3–7.
Levin A, Chaudhry MR, Djurdjev O, Beaulieu M, Komenda P: Diabetes,
Shoji A, Yamanaka H, Kamatani N: A retrospective study of the
kidney disease and cardiovascular disease patients. Assessing care of
relationship between serum urate level and recurrent attacks of gouty
complex patients using outpatient testing and visits: additional metrics
arthritis: evidence for reduction of recurrent gouty arthritis with
by which to evaluate health care system functioning. Nephrol Dial
antihyperuricemic therapy. Arthritis Rheum 2004, 51:321–325.
Transplant 2009, 24:2714–2720.
Product Information. Zylorim™ (Allopurinol) tablets:
Manns BJ, Mendelssohn DC, Taub KJ: The economics of end-stage renal
disease care in Canada: incentives and impact on delivery of care.
Stamp LK, O'Donnell JL, Zhang M, James J, Frampton C, Barclay ML,
Int J Health Care Finance Econ 2007, 7:149–169.
Chapman PT: Using allopurinol above the dose based on creatinine
Alberta Kidney Disease Network:
clearance is effective and safe in patients with chronic gout, including
The BC Renal Agency:
those with renal impairment. Arthritis Rheum 2011, 63:412–421.
Advancing Kidney Care and Research in Canada: Available at:
Longo G, Strinati R, Poli F, Fumi F: Genetic factors in nonspecific bronchial
hyperreactivity. An epidemiologic study. Am J Dis Child 1987, 141:331–334.
Matsushita K, Ballew SH, Astor BC, Jong PE, Gansevoort RT, Hemmelgarn BR,
Sibbald B: T-WM: Factors influencing the prevalence of asthma among
Levey AS, Levin A, Wen CP, Woodward M, Coresh J, Chronic Kidney Disease
first degree relatives of extrinsic and intrinsic asthmatics. Thorax 1979,
Prognosis C: Cohort profile: the Chronic Kidney Disease Prognosis
Consortium. Int J Epidemiol 2013, 42:1660–1668.
Weinmayr G, Weiland SK, Bjorksten B, Brunekreef B, Buchele G, Cookson WO,
Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, Arima H,
Garcia-Marcos L, Gotua M, Gratziou C, van Hage M, von Mutius E, Riikjarv MA,
Chadban SJ, Cirillo M, Djurdjev O, Green JA, Heine GH, Inker LA, Irie F,
Rzehak P, Stein RT, Strachan DP, Tsanakas J, Wickens K, Wong GW, Group IPTS:
Ishani A, Ix JH, Kovesdy CP, Marks A, Ohkubo T, Shalev V, Shankar A,
Atopic sensitization and the international variation of asthma symptom
Wen CP, de Jong PE, Iseki K, Stengel B, Gansevoort RT, Levey AS,
prevalence in children. Am J Respir Crit Care Med 2007, 176:565–574.
Consortium CKDP: Decline in estimated glomerular filtration rate
Law MMJ, Wald N, Luczynska C, Burney P: Changes in atopy over a quarter
and subsequent risk of end-stage renal disease and mortality.
of a century, based on cross sectional data at three time periods.
JAMA 2014, 311:2518–2531.
BMJ 2005, 330:1187–1188.
Smith E, Hoy D, Cross M, Merriman TR, Vos T, Buchbinder R, Woolf A,
Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, Williams
March L: The global burden of gout: estimates from the Global
H, Group IPTS: Worldwide time trends in the prevalence of symptoms of
Burden of Disease 2010 study. Ann Rheum Dis 2014,
asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC
Lopez et al. BMC Medicine 2014, 12:200
Phases One and Three repeat multicountry cross-sectional surveys.
Leon DA, Chenet L, Shkolnikov V, Zakharov S, Shapiro J, Rakhmanova G,
Lancet 2006, 368:733–743.
Vassin S, McKee M: Huge variation in Russian mortality rates 1984–1994:
Asher MI, Pattemore PK, Harrison AC, Mitchell EA, Rea HH, Stewart AW, Woolcock AJ:
artefact, alcohol, or what? Lancet 1997, 350:383–388.
International comparison of the prevalence of asthma symptoms and
Pridemore WA, Chamlin MB, Kaylen MT, Andreev E: The effects of the,
bronchial hyperresponsiveness. Am Rev Respir Dis 1988, 138:524–529.
Russian alcohol policy on alcohol-related mortality: an interrupted time
Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S, International Study of A,
series analysis. Alcohol Clin Exp Res 2006, 2014:257–266.
Allergies in Childhood Phase Three Study G: Global variation in the prevalence
Fillmore KM, Roizen R, Farrell M, Kerr W, Lemmens P: Wartime Paris,
and severity of asthma symptoms: phase three of the International Study of
cirrhosis mortality, and the ceteris paribus assumption. J Stud Alcohol
Asthma and Al ergies in Childhood (ISAAC). Thorax 2009, 64:476–483.
2002, 63:436–446.
Sembajwe G, Cifuentes M, Tak SW, Kriebel D, Gore R, Punnett L: National
Dills AK, Miron JA: Alcohol prohibition and Cirrhosis. Am L & Econ Rev
income, self-reported wheezing and asthma diagnosis from the World
2004, 6:285–318.
Health Survey. Eur Respir J 2010, 35:279–286.
Holmes J, Meier PS, Booth A, Guo Y, Brennan A: The temporal relationship
Van Niekerk CH, Weinberg EG, Shore SC, Heese HV, Van Schalkwyk J:
between per capita alcohol consumption and harm: a systematic review
Prevalence of asthma: a comparative study of urban and rural Xhosa
of time lag specifications in aggregate time series analyses. Drug Alcohol
children. Clin Allergy 1979, 9:319–314.
Depend 2012, 123:7–14.
Keeley DJ, Neil P, Gal ivan S: Comparison of the prevalence of reversible
Babor T, Caetano R, Casswell S, Edwards G, Giesbrecht N, Graham K,
airways obstruction in rural and urban Zimbabwean children. Thorax 1991,
Grube J, Gruenewald P, Hill L, Holder H, Homel R, Livingston M,
Österberg E, Rehm J, Room R, Rossow I: Alcohol: No ordinary
Calvert J, Burney P: Ascaris, atopy, and exercise-induced bronchoconstriction
commodity. Research and public policy. 2nd edition. Oxford and
in rural and urban South African children. J Al ergy Clin Immunol 2010,
London: Oxford University Press; 2010.
Rehm J, Shield KD, Rehm MX, Gmel G, Frick U: Modelling the impact of
Obaseki D, Potts J, Joos G, Baelum J, Haahtela T, Ahlstrom M, Matricardi P,
alcohol dependence on mortality burden and the effect of available
Kramer U, Gjomarkaj M, Fokkens W, Makowska J, Todo-Bom A, Toren K,
treatment interventions in the European Union. Eur
Janson C, Dahlen SE, Forsberg B, Jarvis D, Howarth P, Brozek G, Minov J,
Neuropsychopharmacol 2013, 23:89–97.
Bachert C, Burney P, excellence GLno: The relation of airway obstruction to
Rehm J, Roerecke M: Reduction of drinking in problem drinkers and
asthma, chronic rhinosinusitis and age: results from a population survey of
all-cause mortality. Alcohol Alcohol 2013, 48:509–513.
adults. Allergy 2014, 69:1205–1214.
Nutt DJ, Rehm J: Doing it by numbers: a simple approach to reducing
Asthma GGIf: Available at: . Accessed 6/20, 2014.
the harms of alcohol. J Psychopharmacol 2014, 28:3–7.
Ait-Khaled NED, Bissell K, Billo NE: Access to inhaled corticosteroids is key
Degenhardt LWH, Ferrari AJ, Baxter AJ, Charlson FJ, Hall WD, Freedman G,
to improving quality of care for asthma in developing countries. Allergy
Burstein R, Johns N, Engell RE, Flaxman A, Murray CJ, Vos T: Global burden
2007, 62:230–236.
of disease attributable to illicit drug use and dependence: findings from
Burney P, Potts J, Ait-Khaled N, Sepulveda RM, Zidouni N, Benali R, Jerray M,
the Global Burden of Disease Study 2010. Lancet 2013, 382:1564–1574.
Musa OA, El-Sony A, Behbehani N, El-Sharif N, Mohammad Y, Khouri A, Paralija B,
United Nations Office on Drugs and Crime:
Eiser N, Fitzgerald M, Abu-Laban R: A multinational study of treatment failures
in asthma management. Int J Tuberc Lung Dis 2008, 12:13–18.
WHO causes of death 2000 – 2011:
Volkow ND, Wang GJ, Fowler JS, Tomasi D: Addiction circuitry in the
human brain. Annu Rev Pharmacol Toxicol 2012, 52:321–336.
WHO projections for 2015 and 2030:
Amato LDM, Vecchi S, Ali R, Farrel M, Faggiano F, Foxcroft D, Ling W, Minozzi
S, Chengzheng Z: Cochrane systematic reviews in the field of addiction:
Talwalkar JA, Kamath PS: Influence of recent advances in medical management
what's there and what should be. Drug Alcohol Depend 2011, 113:96–103.
on clinical outcomes of cirrhosis. Mayo Clin Proc 2005, 80:1501–1508.
Sousa RM, Ferri CP, Acosta D, Albanese E, Guerra M, Huang Y, Jacob KS,
Liang W, Chikritzhs T, Pascal R, Binns CW: Mortality rate of alcoholic liver
Jotheeswaran AT, Rodriguez JJ, Pichardo GR, Rodriguez MC, Salas A, Sosa AL,
disease and risk of hospitalization for alcoholic liver cirrhosis, alcoholic
Williams J, Zuniga T, Prince M: Contribution of chronic diseases to disability in
hepatitis and alcoholic liver failure in Australia between 1993 and 2005.
elderly people in countries with low and middle incomes: a 10/66 Dementia
Intern Med 2011, 41:34–41.
Research Group population-based survey. Lancet 2009, 374:1821–1830.
Roberts SE, Goldacre MJ, Yeates D: Trends in mortality after hospital
Sousa RMFC, Acosta D, Guerra M, Huang Y, Jacob K, Jotheeswaran A,
admission for liver cirrhosis in an English population from 1968 to 1999.
Hernandez MA, Liu Z, Pichardo GR, Rodriguez JJ, Salas A, Sosa AL, Williams J,
Gut 2005, 54:1615–1621.
Zuniga T, Prince M: The contribution of chronic diseases to the prevalence of
Schmidt LA, Mäkelä P, Rehm J, Room R: Alcohol: equity and social
dependence among older people in Latin America, China and India: a 10/66
determinants. In Equity, Social Determinants and Public Health Programmes.
Dementia Research Group population-based survey. BMC Geriatr 2010, 10.
Edited by Blas E, Kurup AS. Geneva, Switzerland: World Health Organization;
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP: The global
prevalence of dementia: a systematic review and metaanalysis.
Rehm J, Samokhvalov AV, Shield KD: Global burden of alcoholic liver
Alzheimers Dement 2013, 9:63–75. e62.
diseases. J Hepatol 2013, 59:160–168.
Wimo A, Jonsson L, Bond J, Prince M, Winblad B: Alzheimer Disease I: the
World Health Organization: Global status report on alcohol and health.
worldwide economic impact of dementia 2010. Alzheimers Dement 2013,
Geneva, Switzerland: World Health Organization; 2014.
9:1–11. e13.
Rehm J, Taylor B, Mohapatra S, Irving H, Baliunas D, Patra J, Roerecke M:
Rocca WA, Petersen RC, Knopman DS, Hebert LE, Evans DA, Hall KS, Gao S,
Alcohol as a risk factor for liver cirrhosis - a systematic review and
Unverzagt FW, Langa KM, Larson EB, White LR: Trends in the incidence and
meta-analysis. Drug Alcohol Rev 2010, 29:437–445.
prevalence of Alzheimer's disease, dementia, and cognitive impairment
Vernon G, Baranova A, Younossi ZM: Systematic review: the epidemiology
in the United States. Alzheimers Dement 2011, 7:80–93.
and natural history of non-alcoholic fatty liver disease and non-alcoholic
Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, Brayne C,
steatohepatitis in adults. Aliment Pharmacol Ther 2011, 34:274–285.
Medical Research Council Cognitive F, Ageing C: A two-decade comparison
Perz JF, Armstrong GL, Farrington LA, Hutin YJF, Bell BP: The contributions
of prevalence of dementia in individuals aged 65 years and older from
of hepatitis B virus and hepatitis C virus infections to cirrhosis and
three geographical areas of England: results of the Cognitive Function and
primary liver cancer worldwide. J Hepatol 2006, 45:
Ageing Study I and II. Lancet 2013, 382:1405–1412.
Zatonski W, Sulkowska U, Manczuk M, Rehm J, Lowenfels AB, La Vecchia C:
Qiu C, von Strauss E, Backman L, Winblad B, Fratiglioni L: Twenty-year
Liver cirrhosis mortality in Europe, with special attention to central and
changes in dementia occurrence suggest decreasing incidence in central
eastern Europe. Eur Addict Res 2010, 16:193–201.
Stockholm, Sweden. Neurology 2013, 80:1888–1894.
Ye Y, Kerr WC: Alcohol and liver cirrhosis mortality in the United States:
Schrijvers EM, Verhaaren BF, Koudstaal PJ, Hofman A, Ikram MA, Breteler
comparison of methods for the analyses of time-seriespanel data
MM: Is dementia incidence declining?: Trends in dementia incidence
models. Alcohol Clin Exp Res 2011, 35:108–115.
since 1990 in the Rotterdam Study. Neurology 2012, 78:1456–1463.
Lopez et al. BMC Medicine 2014, 12:200
Stampfer MJ: Cardiovascular disease and Alzheimer's disease: commonlinks. J Intern Med 2006, 260:211–223.
Lincoln P, Fenton K, Alessi C, Prince M, Brayne C, Wortmann M, Patel K,Deanfield J, Mwatsama M: The Blackfriars Consensus on brain healthand dementia. Lancet 2014, 383:1805–1806.
100. Jagger C, Matthews R, Lindesay J, Robinson T, Croft P, Brayne C: The effect of
dementia trends and treatments on longevity and disability: a simulationmodel based on the MRC Cognitive Function and Ageing Study (MRCCFAS). Age Ageing 2009, 38:319–325. discussion 251.
101. Barnes DE, Yaffe K: The projected effect of risk factor reduction on
Alzheimer's disease prevalence. Lancet Neurol 2011, 10:819–828.
102. Norton SMF, Barnes DE, Yaffe K, Brayne C: Potential for primary prevention of
Alzheimer's disease: an analysis of population-based data. Lancet Neurol2014, 13:788–794.
doi:10.1186/s12916-014-0200-8Cite this article as: Lopez et al.: Remembering the forgotten non-communicablediseases. BMC Medicine 2014 12:200.
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Imaging Appendix: Standardization, quality assurance (IMAGE-QA) and Imaging-assisted Management The IMAGE-HF QA program aims to standardize several important aspects of the proposed clinical imaging research: 1. defining best current imaging practice for standard-care tests 2. disseminating advanced imaging technology and standards 3. promoting structured reporting and comprehensive imaging QA 4. ensuring consistent interpretation and patient management recommendations
Detecting Bacillus Spores by Raman and Surface-Enhanced Raman Spectroscopy (SERS) Raman spectroscopy has been employed to detect Bacillus cereusspores, an anthrax surrogate, collected from a letter as it passed Intensity (arbitrary units) through a mail sorting system. Raman spectroscopy also has the capability to identify many common substances used as hoaxes. A