higher CD4 thresholds remains unclear but enthusiasm consequences of interrupting therapy. The Trivacan and for that approach is likely to wane.5,6 One recent large
SMART studies provide a quantitative risk assessment of
randomised clinical study of starting and stopping at CD4
the consequences of stopping therapy and are therefore
cell counts above 350/µL revealed only slightly increased important studies for all treating clinicians. The task at risk of minor HIV-related complications in the interruption hand now is to ensure that all patients—including those in arm (Staccato; table).7
resource-constrained regions, such as West Africa—have
The implications for the individual management of access to well-trained health-care providers who can
anti retroviral therapy level are less clear. Because of readily adopt emerging data into any decision regarding the Trivacan and SMART studies, the most recent US when (if ever) to stop antiretroviral therapy. Department of Health and Human Services guidelines state that treatment interruptions should be avoided Steven G Deeksin clinical practice and should only be done in a closely
San Francisco General Hospital, San Francisco, California 94110, USA
monitored clinical trial.8 However, this is not practical
because many patients in clinical practice have signiﬁ cant
I have received research support or honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Pﬁ zer, Roche, Tibotec, and Trimeris.
side-eﬀ ects, pill fatigue, or treatment fail ure. Presumably
Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine,
any study that speciﬁ cally focuses on those with strong
and lamivudine in adults with human immunodeﬁ ciency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337: 734–39.
reasons to stop therapy might show a beneﬁ t (or at least
Levy AR, James D, Johnston KM, et al. The direct costs of HIV/AIDS care.
a lack of harm) in going on and oﬀ therapy.
Lancet Infect Dis 2006; 6: 171–77.
Danel C, Moh R, Minga A, for the Trivacan ANRS 1269 trial group. CD4-guided
The fundamental challenge raised by Trivacan and
structured antiretroviral treatment interruption strategy in HIV-infected
SMART is how to translate data from broad heterogeneous
adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet 2006; 367: 1981–86.
study populations to an individual. For patients who are
El-Sadr W, Neaton J, for the SMART Study Investigators. Episodic CD4 guided use of antiretroviral therapy is inferior to continuous therapy: results of the
doing well on a stable regimen, the Trivacan and SMART
SMART study. 13th Conference on Retroviruses and Opportunistic Infections.
data clearly indicate that uncontrolled HIV replication is
Denver, Colarado, USA; Feb 5–8, 2006: 106LB (abst).
Maggiolo F, Ripamonti D, Gregis G, Quinzan G, Callegaro A, Suter F. Eﬀ ect of
more harmful than modern treatment regimens, and that
prolonged discontinuation of successful antiretroviral therapy on CD4 T cells:
well-tolerated drugs should be continued indeﬁ nitely.
a controlled, prospective trial. AIDS 2004; 18: 439–46.
Cardiello PG, Hassink E, Ananworanich J, et al. A prospective, randomized trial
This ﬁ nding is not surprising and was widely accepted
of structured treatment interruption for patients with chronic HIV type 1
even before these studies were done (at least it pertains
infection. Clin Infect Dis 2005; 40: 594–600.
Ananworanich J, Gayet-Ageron A, Le Braz M, et al. Program and abstracts of
to regions where treatment is widely available). At what
the 13th Conference on Retroviruses and Opportunistic Infections. Denver, Colarado, USA; Feb 5–8, 2006: 102 (abst).
point the harm associated with treatment in an individual
Panel on Clinical Practices for Treatment of HIV Infection convened by the
outweighs the harm associated with uncontrolled
Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. May 4, 2006:
HIV replication requires a careful understanding of
treatment-related side-eﬀ ects, HIV pathogenesis, and the
Delayed cord clamping increases infants’ iron stores
See Articles page 1997
It is startling to see how a seemingly insubstantial change
Chaparro and colleagues’ international interdisciplinary
in practice might aﬀ ect long-term results for infants.
study with 358 randomised infants shows that waiting
When a medical text recommended immediate cord clam-
2 min before clamping the umbilical cord provided
p ing in 1913, science was in its infancy and expert opinion the infants with more body iron at 6 months of age guided practice. Today, we have the beneﬁ t of scientiﬁ c
without causing any harm at birth. The rationale for the
evidence to advise our actions. The article in today’s Lancet
study—the link between iron deﬁ ciency in infancy and
by Camila Chaparro and colleagues1 provides additional
neurodevelopmental delays—is well founded. The number
weight to the growing evidence that our haste to clamp
of infants in the study was ambitious and the protocol
the umbilical cord and pass the baby oﬀ is ill-advised. The
for the 6-month follow-up was meticulously planned.
mounting evidence that delayed cord clamping beneﬁ ts
The exclusion criteria were carefully selected to rule out
both term and preterm infants continues to build.2,3
women with conditions that negatively aﬀ ect neonates.
www.thelancet.comVol 367 June 17, 2006
Most importantly, the team used multiple methods for identifying the main outcome variable of iron status at 6 months of age. There were no diﬀ erences between the groups of infants on the concerns about harm: neonatal jaundice or polycythaemia. The protocol required that obstetricians and midwives wait up to 2 min to clamp and
We do not have the rights to
cut the umbilical cord. Studies in which cord clamping was
reproduce this image on the
delayed for 3 min or longer also failed to show harm with the assigned delay in cord clamping.2
Infants with delayed cord clamping in Dewey and
colleagues’ study were held level with the mother’s body during the 2-min wait. Lowering the infant can speed the transfusion.4 In our randomised trial of a brief delay (30–45 s) in cord clamping at preterm births, we lowered
the infant below the introitus or incision to hasten transfusion.5 However, if one places the infant on the
that those magical stem cells found in cord blood have
mother’s abdomen brieﬂ y before cutting the cord, the
multiple protective and preventive roles to play in an
infant might receive less placental transfusion.6
infant’s developing body.10 We support the American
The results of Chaparro and colleagues’ study suggest Academy of Pediatrics’ statement which does not
that a modiﬁ cation might be indicated in the active recommend cord-blood collection and storage unless management of the third-stage programme for there is a known family need.11 However, that valuable developing countries, in which anaemia in infancy is cord blood should not be medical waste—let the infants often endemic. Active management of the third stage
prevents maternal haemorrhage after birth. As deﬁ ned
This excellent study by Chaparro and colleagues, the
initially and researched, the process involved three largest ever done on delayed cord clamping with long-steps: (1) a drug is used to contract the uterus; (2) the
term follow-up, adds important evidence in favour of
cord is clamped immediately; and (3) traction is applied delayed cord clamping at the births of term infants. to the cord to speed delivery of the placenta. The most important part of active management is getting the *Judith Mercer, Debra Erickson-Owensuterus to contract to avoid uterine atony. There is a fear University of Rhode Island College, College of Nursing, Kingston, that giving the drug to contract the uterus (uterotonic)
with the infant still attached to the umbilical cord would We declare that we have no conﬂ ict of interest.
cause “overtransfusion.” Yao and co-workers showed 1 Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Liz Cedillo R,
that giving such a drug and delaying cord clamping did
Dewey KG. Eﬀ ect of timing of umbilical cord clamping on iron status in
not result in overtransfusion because the blood volumes
Mexican infants: a randomised controlled trial. Lancet 2006; 367: 1997–2004.
of the infants in this study never went above 90 mL/kg, 2
van Rheenen P, Brabin B. Late umbilical cord-clamping as an intervention for reducing iron deﬁ ciency anaemia in term infants in developing and
even with a 5–6-min wait to clamp.7 Two of the large
industrialised countries: a systematic review. Ann Trop Paediatr 2004; 24:
studies on active management of the third stage reported
Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord
that infants who had immediate cord clamping weighed
clamping in preterm infants. Cochrane Database Syst Rev 2004; 4:
substantially less than the infants who had delayed
Yao AC, Lind J. Eﬀ ect of gravity on placental transfusion. Lancet 1969; 2:
cord clamping.8,9 We believe that more research on the
use of uterotonic drugs while leaving the cord intact is 5
Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular
hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006; 117: 1235–42.
Chaparro and colleagues’ study increases concern 6 Grisaru D, Deutsch V, Pick M, et al. Placing the newborn on the maternal
about the ethics of routine cord-blood collection without
abdomen after delivery increases the volume and CD34 cell content in the umbilical cord blood collected: an old maneuver with new applications.
adequate informed consent and the advertisement
Am J Obstet Gynecol 1999; 180: 1240–43.
of cord blood as “medical waste.” It is very plausible 7
Yao AC, Hirvensalo M, Lind J. Placental transfusion-rate and uterine contraction. Lancet 1968; 1: 380–83.
www.thelancet.comVol 367 June 17, 2006
Rogers J, Wood J, McCandlish R, Ayers S, Truesdale A, Elbourne D. Active
10 Ende N, Reddi AS. Administration of human umbilical cord blood to low birth
versus expectant management of third stage of labour: the Hinchingbrooke
weight infants may prevent the subsequent development of type 2 diabetes.
randomised controlled trial. Lancet 1998; 351: 693–99. Med Hypotheses 2006; 66: 1157–60.
Prendiville WJ, Harding JE, Elbourne DR, Stirrat GM. The Bristol third stage
American Academy of Pediatrics. Cord blood banking for potential future
trial: active versus physiological management of third stage of labour. BMJ
transplantation: subject review. Pediatrics 1999; 104: 116–18.i.
1988; 297: 1295–300. Racism, socioeconomic deprivation, and health in New Zealand
See Articles page 2005
Inequalities in health are deplored in modern democratic Epidemiological data are essential to the identiﬁ cation of nations and equal opportunities are extolled in principle, inequities, and monitoring eﬀ ectiveness of interventions if not in practice. Through the caste system, slavery, to redress them. colonisation, aristocracy, apartheid, and Nazism, inequal-
Harris and colleagues’ study is of special interest, not
ities were institutionalised. The historical legacy of racism only because empirical research on racism and health and economic inequality of opportunity casts its shadow is rare outside the USA, but because it concerns the even now, and the study by Ricci Harris and colleagues1 in
Māori population, an Indigenous ethnic minority. The
today’s Lancet explores the idea.
term indigenous is usually used to mean a population
Inequalities in health status, disease occurrence, and belonging naturally to a place in the sense of long-term
mortality are shaped by accumulated wealth, material ancestral origins—eg, Aborigine (it might also mean the circumstances, environmental quality, nutrition, a wide majority population—eg, in the UK—as an alternative to range of personal behaviours, genetic inheritance, and the word White).2 health services. Within multiethnic societies, European-
Indigenous populations across the world have poor
origin White populations (henceforth, “White” as per health, and many were decimated and demoralised Bhopal’s glossary2) are characterised by being richer, more
in the colonial era. Compared with other Indigenous
powerful, and enjoying better material circumstances, populations, including Native Americans and Australian environmental quality, and health services than non-White Aborigines, the Māori population largely escaped such ethnic-minority populations. Ethnic-health inequalities in a fate. By contrast with other colonised Indigenous and such societies are inevitable.
migrant ethnic minorities, Māoris are perceived to be
Racism is the belief that some racial, ethnic, religious, highly politically and socially organised, empowered, and
and cultural groups are better than others. This belief, in control. This perception, at least in part, is related to combined with power, leads to actions favouring the negotiated Treaty of Waitangi of 1840 that enshrined the supposedly superior groups. The power to enact Māori rights, and that still plays a major role in governing such beliefs is, currently, mostly in the hands of White relations between Māoris and other New Zealanders.4 populations. Some like to believe racism is unimportant Nonetheless, Māori health is comparatively poor. in modern, industrialised, multiethnic societies, others
Bramley and colleagues5 compared the health
believe that racism is at the heart of ethnic and racial inequalities in New Zealand and the USA, with the disparities in health and health care.3 We need data to
European (eﬀ ectively White) and White population,
respectively, in each of these countries as the point of
Equity is the core ethical principle underpinning equality comparison. They used a wide range of health and health-
of health care. It is based on fairness and justice. Most care indicators. The inequalities were massive—eg, life research studies present data from the White population expectancy in Māori men was 8·9 years less than in as the standard against which to compare minority European men in New Zealand, larger than the 7·4 year groups. Not every inequality shown is an inequity. Ethnic diﬀ erence between American Indian or Alaskan native variations in smoking, for example, are not necessarily and White men in the USA. In virtually every indicator, inequitable but such variations in access to smoking
inequalities were considerable, and greater in New Zealand
cessation services would be. Diﬀ erences in life expectancy
than in US comparisons. The life-expectancy deﬁ cit in
in diﬀ erent ethnic groups are usually inequitable, Australian Aboriginal and Torres Strait Islanders is closer because they mainly result from other social injustices. to 20 years.6 By contrast, mortality diﬀ erences between
www.thelancet.comVol 367 June 17, 2006
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SOMMARIO: 1. Lo spostamento dalla teoria delle fonti alla teoria dell’interpre-tazione. – 2. Il giudice Hercules e il demone di Laplace. – 3. La costitu-zione e il cambiamento del grado di definizione. – 4. Interpretazione eapplicazione. – 5. Che cos’è la disposizione? – 6. Principio di sovrappo-sizione. – 7. «Shut up and calculate»? Per una conclusione non scettica. Lo spo