Comment
ecacy of DENV vaccines and the serological responses 1 Sabchareon A, Wallace D, Sirivichayakul C, et al. Protective ecacy of the
can only be interpreted in the context of prevaccination
immune status. Of children receiving one or more vaccine
doses, 32 dengue episodes among 5292 person-years of
observation (06%) were admitted to hospital compared
with 30 among 2630 person-years (11%) for controls,
a 455% reduction. Parents everywhere will want to
know if dengue vaccination will prevent fatal dengue
shock syndrome. When charts were reviewed, only three
children in the vaccinated group and two in the control
group were judged to have had severe dengue; of these
children, three were aged 10 years or older. Ample recent
data from Thailand document the modal age of severe
dengue leading to hospital admission to be in the vicinity
of 11 years.14 Fortunately, Sano Pasteur has given tetra-
valent dengue vaccine to an additional 30 000 adults
and children, mostly in dengue-endemic countries.1
Results from these ongoing vaccine trials should harden
DENV-specic disease ecacy rates and provide direct
evidence of vaccine ecacy for severe disease. Future
dengue vaccine trials should provide robust evidence of
ecacy against severe disease by selecting populations
weighted to assure inclusion of sucient numbers of at-
risk children.
Scott B Halstead
5824 Edson Lane, Bethesda, MD 20852, USA
halsteads@erols.com
I am a senior scientic adviser for the Dengue Vaccine Initiative (International
Vaccine Institute, Seoul, South Korea). I declare that I have no conicts of interest.
Self-harm behaviour: rethinking physical and mental health
Published Online In The Lancet, Helen Bergen and colleagues1 present
September 18, 2012
http://dx.doi.org/10.1016/
results derived from the Multicentre Study of Self-
S0140-6736(12)61509-8 harm in England, which indicate that self-harm is
See Editorial page 1532 associated with poor physical health as well as mental
See Articles page 1568
health. The ndings are not novel,2 but the work adds
to and reinforces several key points. In their cohort of
30 950 individuals who presented with self-harm at
emergency departments in three regions of England
between 2000 and 2007, mortality from both natural and
external causes (eg, suicides, accidental poisoning, and
accidents) was higher than in the general population for
both male and female patients (standardised mortality
ratio 36, 95% CI 3538). The mean number of years
1536
recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai
schoolchildren: a randomised, controlled phase 2b trial. Lancet 2012;
published online Sept 11. http://dx.doi.org/10.1016/S0140-
6736(12)61428-7.
2 Brady OJ, Gething PW, Bhatt S, et al. Rening the global spatial limits of
dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis
2012; 6: e1760.
3 Alonso PL, Sacarlal J, Aponte JJ, et al. Ecacy of the RTS,S/AS02A vaccine
against Plasmodium falciparum infection and disease in young African
children: randomised controlled trial. Lancet 2004; 364: 141120.
4 Francis DP, Heyward WL, Popovic V, et al. Candidate HIV/AIDS vaccines:
lessons learned from the worlds rst phase III ecacy trials. AIDS 2003;
17: 14756.
5 Monath TP, Cetron MS, Teuwen DE. Yellow fever vaccine. In: Plotkin SA,
Orenstein WA, Ot PA, eds. Vaccines, 5th edn. Philadelphia: Saunders
Elsevier, 2008: 9591055.
6 Halstead SB, Thomas SJ. Japanese encephalitis: new options for active
immunization. Clin Infect Dis 2010; 50: 115564.
7 Murphy BR, Whitehead SS. Immune response to dengue virus and
prospects for a vaccine. Annu Rev Immunol 2011; 29: 587619.
8 Halloran ME, Longini IM, Struchiner CJ. Modes of action and time-varying
VEs. In: The design and analysis of vaccine studies. New York: Springer,
2009: 13152.
9 Capeding RZ, Luna IA, Bomasang E, et al. Live-attenuated, tetravalent
dengue vaccine in children, adolescents and adults in a dengue endemic
country: randomized controlled phase I trial in the Philippines. Vaccine 2011;
29: 386372.
10 Gibbons RV, Kalanarooj S, Jarman RG, et al. Analysis of repeat hospital
admissions for dengue to estimate the frequency of third or fourth dengue
infections resulting in admissions and dengue hemorrhagic fever,
and serotype sequences. Am J Trop Med Hyg 2007; 77: 91013.
11 Guy B, Barban V, Mantel N, et al. Evaluation of interferences between
dengue vaccine serotypes in a monkey model. Am J Trop Med Hyg 2009;
80: 30211.
12 Wahala WM, de Silva AM. The human antibody response to dengue virus
infection. Viruses 2011; 3: 237495.
13 de Alwis R, Smith SA, Olivarez NP, et al. Identication of human
neutralizing antibodies that bind to complex epitopes on dengue virions.
Proc Natl Acad Sci USA 2012; 109: 743944.
14 Cummings DA, Iamsirithaworn S, Lessler JT, et al. The impact of the
demographic transition on dengue in Thailand: insights from a statistical
analysis and mathematical modeling. PLoS Med 2009; 6: e1000139.
of life lost (YLL) for natural-cause deaths was 259 years
(95% CI 257260) for male patients and 255 years
(252258) for female patients. Mean YLL for external-
cause deaths was 402 years (400403) in male patients
and 400 years (397405) for female patients.
Notably, natural-cause mortality was clearly linked to
socioeconomic status (assessed by place of residence),
increasing with economic deprivation ( trend for both
sexes combined 510; p<00001). No such association
was recorded for external-cause mortality (030;
p=058). In addition to what might be expected for
external causes such as suicide and accidental poisoning,
diseases of the digestive and circulatory systems had
www.thelancet.com Vol 380 November 3, 2012

especially heavy burdens, with self-reported alcohol
problems at the time of index self-harm associated with
digestive-system disease and physical health problems
associated with circulatory-system disease. The results
of Bergen and colleagues study1 are interesting in other
aspects. The disparate ages of death from external
causes in Figure 1 strongly suggest that the self-harm
cohort might, in fact, have been heterogeneous in
terms of suicidal intent.1 Additionally, the overall burden
of mortality was greater in male patients (total YLL
34 463 years) than in female patients (22 482 years).
Self-harm is a term favoured in the UK and EU but is
used less in the USA,3 where researchers and clinicians
attempthowever challenging it might be to do soto
distinguish deliberate, self-injurious behaviours with
a suicidal intent from actions that are not suicidal. The
results of Bergen and coworkers study1 could point to
fundamental dierences between subpopulations and
invite consideration of the usefulness of the broad self-
harm category. Prospective studies are undoubtedly
needed to address such issues and future analyses of this
dataset might prove to be informative.
The follow-up period of 210 years and the age of
patients who diedwhether from natural or external
causesimplies that individuals were largely enrolled
during adulthood.1 Much of the self-harm literature
has focused on young people;4,5 related data6 point to a
gradual decline in self-harm behaviours when individuals
pass into adulthood. With a few exceptions,7 this
emphasis on adolescent self-harm behaviours obscures
the mortality burden that largely falls in the middle years
of lifea situation that is readily apparent in the USA.8,9
The most important implication of the study derives
from developmental and public health perspectives.
Bergen and colleagues ndings strongly suggest that
factors contributing to the emergence of self-harm
behaviours and suicide and other causes of death are
often common to those that contribute to premature
deaths from various medical disorders. A so-called
common risk model has been advocated, with the
understanding that suicide is one of several adverse
outcomes that arise from factors that contribute to self-
inicted death.9 For example, alcohol and drug use, family
turmoil, legal cases, school dropout, and subsequent
poor vocational opportunities for adults who have
insucient job skills play a part in premature death (eg,
motor-vehicle accidents, drug overdoses, homicide, and
www.thelancet.com Vol 380 November 3, 2012
Comment
Corbis
suicide) in older adolescents and young adults in the
USA.9 Although predominant cause of death diers by
ethnic origin and sex, the mortality surge that begins
during adolescence is common between many groups.10
In view of Bergen and colleagues data,1 it could be useful
to envision outcomes such as premature medical deaths,
accidental deaths, and suicides as having the same roots
but developing dierently.
For some individualsthose with comorbid psychi-
atric, addiction, and medical disorders for which much
morbidity and mortality is anticipatedalternative care
systems should be developed that are shaped to meet
patients needs, even when patients behaviours do not
conform to the usual way individuals interact with their
health-care providers. Premature deaths in patients
with severe psychiatric disorders are well known.11,12
More than two decades ago, I was part of a team
that developed a primary-care outpatient service in
Rochester, NY, USA, to confront the fact that more than
40% of patients with severe mental disorders discharged
from a psychiatric inpatient service did not attend their
next primary-care medical appointment. The service
was linked to the psychiatric outpatient clinic, such that
case managers, clinicians, or assistants could escort
patients to their medical appointments. With time, care
has become functionally and geographically integrated.
An acute medical inpatient unit was added in 2006,
and was attuned to the needs of patients with severe
comorbid physical and mental disorders, those whose
drug dependency had led to acute systemic diseases,
or those compromised by dementia, delirium, or other
1537
 Comment
complex behavioural challenges that can complicate
inpatient medical treatment.
Apart from emphasising the necessity of integrated
clinical services, the work of Bergen and colleagues1
points to how all clinicians should alter their mindset
when assessing patients who present with self-harming
behaviours. Although review of risk and protective
factors for imminent, potentially fatal suicide attempts
is essential, assessment of the nature of peoples lives
ie, appraisal of the broad contexts of their actions,
social and interpersonal struggles, behaviours, and
basic medical problemsis equally important. For
psychiatrists, Bergen and colleagues ndings call for the
development of so-called public health and preventive
psychiatry.13 They should encourage policy makers to
look for new models of service delivery to meet patients
diverse needs. The ndings invite physicians and their
colleagues to assess the behavioural factors that might
contribute to the early emergence of various medical
disorders. Routine undertaking of such assessments
is the essence of a public health strategy that can be
implemented eciently with careful planning.
Eric D Caine
Department of Psychiatry and Injury Control Research Center for
Suicide Prevention, University of Rochester Medical Center,
Rochester, NY 14624, USA; and Center of Excellence for Suicide
Prevention, Veterans Health Administration Medical Center,
Canandaigua, NY, USA
eric_caine@urmc.rochester.edu
Tobacco control: learning from Uruguay
Published Online In The Lancet, Winston Abascal and colleagues present
September 14, 2012
http://dx.doi.org/10.1016/
ndings from their population-based trend analysis,
S0140-6736(12)61143-X which show a clear decrease in the prevalence of
See Articles page 1575 smoking in Uruguay between 2005 and 2011.1 They
associate this decrease with the far-reaching tobacco
control campaign launched in the country in 2005.
The campaign included actions such as the banning
of tobacco advertising, the banning of smoking in all
enclosed public spaces, tax increases, and legislation
requiring that pictograms with health warnings cover
80% of both the front and back of every cigarette pack.
They recorded annual decreases in all three selected
indicators: a 43% (95% CI 2462) decrease in per-
person tobacco consumption, an 80% (45116)
1538
I declare that I have no conicts of interest.
1 Bergen H, Hawton K, Waters K, et al. Premature death after self-harm:
a multicentre cohort study. Lancet 2012; published online Sept 18. http://
dx.doi.org/10.1016/S0140-6736(12)61141-6.
2 Hawton K, Harriss L, Zahl D. Deaths from all causes in a long-term
follow-up study of 11,583 deliberate self-harm patients. Psychol Med 2006;
36: 397405.
3 Crosby A, Ortega L, Melanson C. Self-directed violence surveillance:
uniform denitions and recommended data elements, version 1.0. Atlanta,
GA: National Center for Injury Prevention and Control, 2011.
4 Hawton K, OConnor RC. Self-harm in adolescence and future mental
health. Lancet 2012; 379: 19899.
5 Hawton K, Saunders KEA, OConnor RC. Self-harm and suicide in
adolescents. Lancet 2012; 379: 237382.
6 Moran P, Coey C, Romaniuk H, et al. The natural history of self-harm from
adolescence to young adulthood: a population-based cohort study.
Lancet 2012; 379: 23643.
7 Hawton K, Harriss L. Deliberate self-harm in people aged 60 years and over:
characteristics and outcome of a 20-year cohort. Int J Geriatr Psychiatry
2006; 21: 57281.
8 Knox K, Caine E. Establishing priorities for reducing suicide and its
antecedents in the United States. Am J Pub Health 2005; 95: 1898903.
9 Caine ED, Knox KL, Conwell Y. Public health and population approaches for
suicide prevention. In: Cohen NL, Galea S, eds. Population mental health:
evidence, policy, and public health practice. London: Routledge,
2011: 30338.
10 Centers for Disease Control and Prevention. Web-based injury statistics
query and reporting system. Atlanta, GA: Centers for Disease Control and
Prevention, 2012.
11 Saha S, Chant D, McGrath J. A systematic review of mortality in
schizophrenia: is the dierential mortality gap worsening over time?
Arch Gen Psychiatry 2007; 64: 112331.
12 Hoang U, Stewart R, Goldacre MJ. Mortality after hospital discharge for
people with schizophrenia or bipolar disorder: retrospective study of linked
English hospital episode statistics, 19992006. BMJ 2011; 343: d5422.
13 Caine ED. Preventing suicide is hard to do! Psychiatr Serv 2010; 61: 1171.
decrease in adolescent smoking prevalence, and a 33%
(2441) decrease in adult tobacco-use prevalence. For
all three indicators, recorded decreases were much larger
in Uruguay than they were in Argentina, the country the
investigators chose as a control. These ndings conrm
the outstanding and consistent progress made by
Uruguays anti-tobacco policy.
Abascal and colleagues study reinforces two im-
portant factors for tobacco control. The rst is the
eect of the international initiative culminating in the
Framework Convention on Tobacco Control (FCTC),2
which has been ratied by 175 countries.3 The second is
the need to use evidence-based approaches, as done in
their study, to assess tobacco-control actions.
www.thelancet.com Vol 380 November 3, 2012