October 2011

*OYPZ[PUH3H\
A
ixaban is suerior lo varfarin
in revenling slroke or syslemic
embolism in alienls vilh alrial
hbrillalion (AI), according lo resulls of lhe
inlernalional ARISTTLL* lrial resenled
recenlly al lhe 2O11 Luroean Sociely of Car-
diology Congress in Iaris, Irance.
The resulls, hailed as lhe mosl osilive
so far for nev oral anlicoagulanls in AI,
also shoved signihcanlly reduced ma|or
bleeding and morlalily vilh lhe lvice-daily
faclor Xa inhibilor comared vilh varfa-
rin. |N |ng| j Mc! 2O11, DI: 1O.1O561NL}-
Moa11O7O39j
In lhe randomized double-blind lrial, in-
vesligalors comared aixaban (5 mg lvice
daily) vilh varfarin (largel INR |Inlerna-
lional Normalized Ralioj, 2.O3.O) in 18,2O1
AI alienls from 39 counlries vho had al
leasl one addilional risk faclor for slroke.
The rimary efhcacy oulcome vas reduc-
lion of ischemic or hemorrhagic slroke or
syslemic embolism, vhile lhe rimary safe-
ly oulcome vas ma|or bleeding according lo
lhe Inlernalional Sociely of Thrombosis and
Hemoslasis (ISTH) dehnilion.
Al a median follov-u of 1.8 years,
aixaban signihcanlly reduced lhe relalive
risk of slroke or syslemic embolism by 21
ercenl. The annual evenl rales vere 1.27
ercenl for aixaban vs 1.6O ercenl for
varfarin, said Dr. Lars Wallenlin of lhe U-
sala Universily in Usala, Sveden.
The effecl on slroke vas redominanlly
driven by a 49 ercenl reduclion in hemor-
rhagic slroke comared vilh varfarin.
Moreover, lhe relalive risks of ISTH ma-
New ora| anticoagu|ant
outshines warfarin in AF
1urn ic pcgc 9 >>
:HYHZ9HTP`H
C
hildhood abuse is linked lo mullile
and long-lasling deressive eisodes,
according lo a nev rilish sludy.
The research, led by a leam al King's
College London Inslilule of Isychialry, also
found lhal abused individuals are more
likely lo resond oorly lo harmacological
and sychological lrealmenl for deression.
|Am j Psqcnicirq 2O11 Aug 14. Lub ahead of
rinlj
Senior invesligalor Dr. Andrea Danese
said: Idenlifying lhose al risk of mullile
and long-lasling deressive eisodes is cru-
cial from a ublic heallh erseclive. The re-
sulls indicale lhal childhood mallrealmenl is
associaled bolh vilh an increased risk of de-
veloing recurrenl and ersislenl eisodes
of deression, and vilh an increased risk of
resonding oorly lo lrealmenl.
Therefore, he said revenlion and early
lheraeulic inlervenlions largeling child-
hood abuse may revenl lhe ma|or heallh
burden caused by deression. Iurlhermore,
Abused chi|dren prone to |ong-term depression
1urn ic pcgc 4 >>
FORUM
2
Quality and patient safety: Is
the glass half full or half empty?
CONFERENCE
8
Secondary CVD preventive
meds underused
I N PRACTI CE
38
Managing chronic
constipation in primary care
Apixc|cn pcrjcrmc! |ciicr incn ucrjcrin in sirckc cn! sqsicmic cm|c|ism prctcniicn.
www.medica|tribune.com
SGP.284.11.06.07
For prescribing information, please contact:
sanofi-aventis (Singapore) Pte Ltd.
6 Raffles Quay #18-00 Singapore 048580
Tel: +65 6226 3836 Fax: +65 6334 2539
NOW AVAILABLE

ver lhe asl 1O years, lhe HMA has

broadened ils focus on alienl care
lo include, nol |usl qualily, bul a-
lienl safely.
Qualily managemenl, lolal qualily man-
agemenl, conlinuous qualily imrovemenl
and hnancial managemenl are ersislenl
lhemes in alienl care lileralure over lhe asl
1O years.
Thinking aboul qualily and alienl safe-
ly is coming logelher, vilh lhe lvo concels
in arlnershi ralher lhan as searale disci-
lines, and lhey are increasingly linked in
lhe same hrases.
ul is lhe glass half full or half emly
vhen il comes lo lhe fulure of alienl care`
In an arlicle from lhe Icncci |ournal in
1999, Dr. Cyril Chanller, nov chair of Uni-
versily College London Iarlners in lhe UK,
said medicine used lo be simle, inef-
feclive and safe. Nov il's comlex, effec-
live and olenlially dangerous. |Icncci
1999,353(9159):1178-81j
Chanller describes lhe silualion loday as
vell as he did more lhan 1O years ago.
Aiming lo close lhe qualily chasm, a re-
orl from lhe Inslilule of Medicine (IM) in
1999, enlilled 'To Lrr is Human: uilding A
Safer Heallh Syslem', shoved lhal, collec-
lively, 98,OOO alienls vere harmed in US
hosilals.
Il is likely lhal 1O-15 ercenl of all hosi-
lal admissions around lhe vorld end in some
kind of revenlable harm lo lhe alienl.
Among lhe goals laid dovn by lhe IM
vas a roosal lo reduce hosilal errors by
5O ercenl over lhe subsequenl 5 years, bul
vas lhis accomlished`
In an arlicle for lhe Briiisn Mc!icc| jcur-
nc| called 'Is Heallhcare Gelling Safer`' |BMj
2OO8,337:a2426. DI: 1O.11361bm|.a2426j, Dr.
Charles Vincenl of Imerial College London
said lhe lack of reliable informalion on safe-
ly and qualily of care is hindering imrove-
menl and safely across lhe vorld.
Dr. Roberl Waclher of lhe Universily of
California, San Irancisco Medical Cenler
in lhe US reorled lhal lhe US heallhcare
induslry did nol imrove enough in lhe 1O
years since lhe IM reorl vas released
relalive lo lhe original goals. He noled lhe
mosl slriking imrovemenls vere in reorl-
ing and leadershi, bul lhal gas in infor-
malion lechnology and accounlabilily vere
a rimary concern. |Hcc|in Ajj (Mi||ucc!)
2O1O,29(1):165-73j
Unforlunalely, lhe IM sludy cannol be
reealed as il is imossible lo have similar
dala every 5 years and lhe business frame-
vork for such research isn'l available yel.
uilding lhe business case has relied on
looking al liabilily exosure, lhe number of
claims, lhe dollar amounl of lhe claims and
rocess efhciency. And ve resume lhal
vhen rocesses are efhcienl lhey save mon-
ey.
ul moslly ve imrove rocesses vilh-
oul allaching hnancial melrics, so lhere is
very scanl dala on efhciency and relurn on
inveslmenl.
We also resume beller lechnology
makes rocesses more efhcienl and safer.
Hovever, for examle, some comulerized
drug order syslems fail lo relurn drug safely
alerls on dose limilalions, conlraindicalions,
drug inleraclions, allergies and olher lhreals
lo alienl safely.
Have ve ul loo much reliance on lech-
nology vhen lhal could roduce a hosl of
alienl safely issues` Safe inlroduclion of
nev lechnology for alienls is an imorlanl
area lo reviev as ve look al nev syslems.
There have been some successes. Regu-
lalory aroaches and accredilalion syslems
have been inlernalionally successful. Local
governmenls have been exemlary in lhese
areas, heling lo crafl regulalions, slimulal-
ing dala colleclion and assing dala back
lo collecling organizalions. Il has robably
been lhe mosl overful force in shaing our
underslanding of qualily and alienl safely.
Neverlheless, vrong alienl, vrong sile
surgeries occur every day in hosilals. Iro-
cedural noncomliance is one of lhe lo
causes of alienl safely incidenls.
ul lhere are reasons lo believe lhe glass
of qualily and alienl safely is half full.
Heallh lanning has shifled from being
reaclive involving qualily assurance and
more unilive aclion lo considering ro-
cesses and syslems. Nov, roaclive lanning
focuses on less syslem failure and vhal il
means lo be suslainable.
In his Sviss cheese model of safely
incidenls, Dr. }ames Reason of lhe Univer-
sily of Manchesler in lhe UK described hov
heallhcare syslems can be like slacks of sviss
cheese slices, full of holes. Iocusing roblem
solving energy al lhe bollom holes revenls
near misses, |usl before some lrigger evenl
lhal resulls in a failure for a alienl. |BMj
2OOO,32O(7237):768-7Oj
High reliabilily organizalions focus on
lhe olher end, vhere slighl, re-lrigger dif-
ferences can revenl a series of lases and
lalenl failures. And lhe mosl dislinguish-
ing asecl aboul such organizalions is lhe
leadershi commilmenl. Il is very difhcull
lo make enlire organizalions highly reliable.
ul focusing on being reliable and embrac-
ing il as arl of lhe vork cullure can imrove
organizalions.
Thoughl leaders in qualily movemenl
believe lhal academics and induslry leaders
should embrace lhe business case for qualily
and focus on lhe nexus of qualily and cosl
over lhe nexl 5O years.
Qualily imrovemenl and alienl safely
inilialives have hislorically been a hard sell
for hysicians bul nov lhere are more hysi-
cian led inilialives lo gel rid of overuse, lo
revenl comlicalions, and lo slreamline
Qua|ity and patient safety: ls the
g|ass ha|f fu|| or ha|f empty!
Exccrptcd Irnm a prcscntatInn by Dr. PauI tanOsIenberg, vIcc prcsIdcnt nI IntcrnatInna!
AccrcdItatInn, Standards and Mcasurcmcnt Inr JnInt CnmmIssInn IntcrnatInna!, durIng thc
10th HnspIta! Managcmcnt AsIa (HMA) cnnIcrcncc, hc!d rcccnt!y In SIngapnrc.
Mcsi ncc|inccrc ucrkcrs ui|| imprctc ij incq nctc inc rigni icc|s ic imp|cmcni simp|c cncngcs.
rocesses, vhich is encouraging lo see.
Qualily is an evolulionary rocess and
lhe lools and slandards for il vill be differ-
enl 2O years from nov. Slandards vill be
lhe louchslone for vhal ve should do and
vhal's righl. All heallhcare delivery, vhelh-
er ve like il or nol, is reelilive and mosl
heallhcare vorkers vill imrove if lhey have
lhe righl lools lo imlemenl simle changes.
Those lhal consider lhe glass half
full see lhal adminislralors have suf-
hcienl lools lo face qualily and alienl
safely challenges nov, bul lhose vho
consider lhe glass half emly recognize
lhal more resulls are slill needed. ur
challenge is lo kee bolh glasses full.
For um
October 2011
02
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Cease giving certain antibiotics, says expert
I
hysicians should immedialely curlail lheir rescrilions of broad seclrum anlibiol-
ics, a microbiologisl has varned.
Narrov seclrum anlibiolics and more largeled drugs should be used inslead, said
Dr. Marlin laser, rofessor of microbiology and chair of lhe dearlmenl of medicine
al Nev York Universily's Langone Medical Cenler, Nev York, US. |Nciurc 2O11, 476:
393394j
The uninlended consequences of anlibiolic use are ermanenl changes in lhe body's
roleclive, friendly ora vhich could harm lhe body's nalural defense syslem, he
varned, adding lhis may be more dangerous lo heallh lhan lhe crealion of drug-resis-
lanl suerbugs.
Scienlisls have found lhal some of lhe benehcial bacleria may never recover and lhal
lhese exlinclions may lead lo increased suscelibilily lo infeclions and disease.
Anlibiolic use could, in facl, be conlribuling lo increases in obesily, allergies and aslh-
ma, inammalory bovel disease, and lye 1 diabeles, said laser.
I believe lhal doclors of lhe fulure vill be relacing 'losl' members of our normal
ora in young children lo diminish lhe risk of develomenl of lhese imorlanl and
chronic diseases.
Coriander's antibacteria| properties
C
oriander seeds may be able lo do much more lhan sice u Indian cuisine.
Researchers from lhe Universily of eira Inlerior in Iorlugal have found lhe oil
of coriander seeds lo be effeclive againsl 12 slrains of bacleria, including |scncricnic cc|i,
Sc|mcnc||c cnicricc, Bcci||us ccrcus and melhicillin-resislanl Sicpnq|cccccus curcus.
Solulions conlaining 1.6/ coriander oil or less reduced grovlh of all lhese slrains in a
lab selling, and mosl vere killed, said lhe researchers. |j Mc! Micrc|ic| 2O11, Lub ahead
of rinlj
The use of coriander oil in foods and in clinical agenls could revenl food-borne ill-
nesses and even lreal anlibiolic-resislanl infeclions, lhey hyolhesized.
This sludy nol only shovs coriander oil's anlibaclerial effecl, bul also rovides an
exlanalion of hov il vorks, vhich vas nol reviously underslood.
The resulls indicale lhal coriander oil damages lhe membrane surrounding lhe bac-
lerial cell. This disruls lhe barrier belveen lhe cell and ils environmenl and inhibils es-
senlial rocesses including resiralion, vhich ullimalely leads lo dealh of lhe baclerial
cell, exlained lhe lead researcher, Dr. Iernanda Domingues.
The researchers nov need lo demonslrale lhal lhe oil can be equally effeclive againsl
harmful alhogens oulside of lhe lab.
Fit and fat may not be a|| that bad

bese individuals vho are olhervise hl and lead a heallhy lifeslyle aear lo live
|usl as long as lheir slim counlerarls, and are also less likely lo die of cardiovas-
cular diseases.
Il's ossible lhal lrying and failing lo lose veighl may be more delrimen-
lal lhan simly slaying al an elevaled body veighl and engaging in a heallhy
lifeslyle lhal includes hysical aclivily and a balanced diel vilh lenly of fruils
and vegelables, said Dr. }ennifer Kuk, assislanl rofessor in York Universily
School of Kinesiology and Heallh Science, Toronlo, Canada.
Kuk and colleagues sludied 6,OOO obese Americans over a 16-year san, comaring
lheir morlalily risk vilh lhal of lean individuals. |App| Pnqsic| Nuir Mcic| 2O11, 36: 57O
576j
They found lhal obese eole vho had no, or only mild, sychological or hysiologi-
cal imairmenls vere haier vilh lheir size and had lried lo lose veighl less oflen.
Hovever, lhese eole vere also more likely lo be hysically aclive and consume a
heallhy diel.
Medi cal Br i ef s
October 2011
03
Prescribing Information PRADAXA

C: Dabigatran etexilate I: Primary prevention of venous

thromboembolic events in adult patients who have undergone
elective total hip or knee replacement surgery. Prevention of stroke
& systemic embolism in patients w/ non-valvular atrial brillation.
D: Prevention of VTE Following elective knee replacement
surgery: Initially 110 mg w/in 1-4 hr of completed surgery, then
220 mg once daily thereafter, for 10 days. Following elective hip
replacement surgery: Initially 110 mg w/in 1-4 hr of completed
surgery, then 220 mg once daily thereafter, for 28-35 days. For both
surgeries, if haemostasis is not secured, initiation of treatment should
be delayed. If the treatment is not started on the day of surgery,
then treatment should be initiated w/ 2 cap once daily. Elderly &
renal impairment (CrCl 30-50 mL/min) Initially 75 mg w/in 1-4 hr
of completed surgery, then 150 mg once daily thereafter. Treatment
should be continued for a total of 10 days after knee replacement
surgery & 28-35 days after hip replacement surgery. Prevention
of stroke & systemic embolism in patients w/ non-valvular
atrial brillation 150 mg bd. Elderly *80 yr, patient at risk of
bleeding 110 mg bd. A: Swallow whole, do not chew/crush. CI:
Severe renal impairment (CrCl <30 mL/min), active clinically
signicant bleeding, organic lesions at risk of bleeding, spontaneous
or pharmacological impairment of haemostasis, hepatic impairment
or liver disease expected to have any impact on survival. Concomitant
treatment w/ systemic ketoconazole. SP: Haemorrhagic risk ie
congenital or acquired coagulation disorders, thrombocytopenia
or functional platelet defects, active ulcerative GI disease, recent
biopsy or major trauma, recent intracranial haemorrhage or brain,
spinal or ophth surgery, bacterial endocarditis; acute renal failure,
moderate renal impairment. Concomitant use w/ drugs that may
increase risk of bleeding. Surgery or invasive procedures; spinal
& epidural anaesth; lumbar puncture; post-procedural period, hip
fracture surgery. Patients at high surgical mortality risk & w/ intrinsic
risk factors for thromboembolic events. Patients <18 yr. Pregnancy
& lactation. AR: Bleeding, anaemia, haemorrhage, haematoma,
haematuria, procedural complications, ALT *3x ULN, decreased
Hb, GI disorders. DI: Unfractionated heparins & heparin derivatives,
LMWH, fondaparinux, desirudin, thrombolytic agents, GPIIb/IIIa
receptor antagonists, clopidogrel, ticlopidine, dextran, sulnpyrazone,
vit K antagonists, amiodarone, verapamil, quinidine, clarithromycin,
ketoconazole, NSAIDs w/ elimination half-life >12 hr; P-glycoprotein
inducers eg rifampicin, St. Johns wort or carbamazepine.
For more information, go to www.pradaxa.com
References
1. Connolly SJ et al. N Engl J Med 2009; 361:11391151.
2. Connolly SJ et al. N Engl J Med 2010; 363:18751876 (letter
to editor).
Introducing Pradaxa

150 mg bid
The rst oral anticoagulant proven to provide
superior stroke prevention vs warfarin
1,2
P
R
A
/2
7
0
9
2
0
1
1
/0
0
1
FOR THE PREVENTION OF STROKE AND SYSTEMIC EMBOLISM IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION
N
O
W

I
N

S
I
N
G
A
P
O
R
E
Simply superior stroke prevention
Boehringer Ingelheim Singapore
Pte Ltd
300 Beach Road #37-00
The Concourse
Singapore 199555
Tel: 6419 8600 Fax: 6299 3083
Introducing Pradaxa

150 mg bid
The rst oral anticoaggulant pproven to pprovide
R THE PREVENTION OF STROKE AND SYSTEMIC EMBOLISM IN PA PP T AA IENTS WITH NON-VALVULAR AT AA RIAL FIBRIL
STROKE PREVENTION
<< |rcm pcgc 1
3LVUHYK@HW
T
argeled monoclonal anli-
body lrealmenls have been
shovn lo imrove lung
funclion and reduce corlicosleroid
dosage in alienls vilh severe and
difhcull-lo-lreal aslhma, says an
exerl.
The ideal lrealmenl for severe
aslhma should imrove lung func-
lion, revenl exacerbalions, reduce
oral sleroid use, and ossess dis-
ease-modifying aclion fealures and
broad-seclrum aclivily, in addi-
lion lo having an accelable safely
rohle, said Irofessor Neil arnes,
of lhe London Chesl Hosilal and
lhe London Trusl and Medical
School, UK.
Three monoclonal anlibody
lrealmenls, omalizumab, kelix-
imab and daclizumab, have been
shovn lo imrove lung funclion
and reduce corlicosleroid usage,
arnes said.
malizumab is a monoclonal
anli-immunoglobulin L (IgL) an-
libody largeled for severe aslhma
inadequalely conlrolled by high-
dose inhaled corlicosleroids (ICS)
and long-acling bela
2
agonisl lher-
ay. The INNVATL sludy found
lhal omalizumab signihcanlly re-
duced severe aslhma exacerbalions
and lhe need for emergency medi-
cal inlervenlions, vilh a 26 ercenl
decrease in aslhma exacerbalions
during a 28-veek lrealmenl eriod
(N419). |A||crgq 2OO5,6O(3):3O9-16j
Keliximab is a monoclonal an-
libody lhal successfully eliminales
CD4 osilive T-cells in severe aslh-
ma alienls. In a blinded sludy,
22 alienls vere assigned varying
doses of keliximab or lacebo. A
signihcanl imrovemenl in lung
funclion vas reorled in lhese
sleroid-deendenl severe aslhma
alienls. Ialienls on keliximab
reorled feeling beller 24 hours
afler receiving lhe dose. |Icncci
1998,352(9134):11O9-13j
Daclizumab is a monoclonal
anlibody lhal binds lo lhe inler-
leukin-2 (IL-2) recelor, inhibil-
ing IL-2 binding. Daclizumab vas
shovn lo have imroved aslhma
conlrol (imroved lung funclion
and reduced deendence on ICS)
in alienls vilh moderale-lo-se-
vere aslhma nol olimally lrealed
by high-dose ICS (N115). |Am j
Rcsp Crii Ccrc 2OO8,178:1OO2-8j
Unforlunalely, arnes said,
omalizumab, keliximab and da-
clizumab do nol have accelable
safely rohles. This limils lhe
number of alienls lhal can be con-
sidered for lhese lheraies. He cau-
lioned lhal lhe secihed drugs are
exensive and have loxicilies lhal
ve do nol vanl lo exose alienls
unnecessarily lo.
There are ockels of alienls
Targeted monoc|ona| antibody therapeutics
for severe, persistent asthma
vho need lo be scrulinized care-
fully for olher underlying condi-
lions like bronchieclasis, reux
mimicking aslhma or hyervenli-
lalion syndrome, he said. Isycho-
logical and sychialric roblems,
in addilion lo drug adherence and
comliance issues, should also be
veighed carefully before adminis-
lering lhese drugs.
No one drug is successful in
conlrolling severe aslhma, arnes
noled, bul nev lrealmenls are in
lhe ieline. Inhaled anli T-cell
lheraies (as oosed lo currenl
inlravenous lheraies) should be
considered olenlial lrealmenls, he
added.
arnes vas seaking al lhe An-
nual Congress of lhe Malaysian
Thoracic Sociely in Kuala Lumur,
Malaysia recenlly.
clinicians can delermine alienls'
rognosis vhen lhey knov lhal
individuals vilh a hislory of abuse
vill nol resond as vell lo lreal-
menl.
Hovever, fulure research
should exlore biological changes
associaled vilh mallrealmenl be-
fore accumulalion of mullile de-
ressive eisodes.
The resulls emerged from a
combined analysis of 16 eide-
miological sludies and 1O clinical
lrials involving more lhan 2O,OOO
and 3,OOO arlicianls, reseclive-
ly.
(UNLSPUL>VVU
T
he resulls of a hase II lrial
suggesl lhal lebrikizumab, a
novel humanized monoclonal an-
libody (Mab) designed lo block
inlerleukin-13 (IL-13) cylokines, is
effeclive in lhe lrealmenl of adull
alienls vilh unconlrolled aslhma.
In lhe MILLY* sludy, vhich in-
volved 219 alienls vilh aslhma,
many of vhom vere unconlrolled
by lheir exisling lheraies, leb-
rikizumab signihcanlly increased
re-bronchodilalor forced exira-
lory volume in 1 second (ILV1)
comared lo lacebo (9.8 ercenl
versus 1.9 ercenl, PO.O2) afler 12
veeks of lrealmenl. |N |ng| j Mc!
2O11 Aug 3. Lub ahead of rinlj
The sludy researchers also
found lhal in lhe lebrikizumab-
lrealed grou, alienls vilh high
re-lrealmenl levels of lhe bio-
marker erioslin had a signihcanl
8.2 ercenl (PO.O3) relalive in-
crease from baseline ILV1 com-
ared lo lacebo. In comarison,
lebrikizumab-lrealed alienls vilh
lov re-lrealmenl erioslin levels
had a nonsignihcanl 1.6 ercenl
relalive increase in ILV
1
comared
lo lacebo.
Ialienls enrolled in lhe sludy
vere dosed subculaneously ev-
ery 28 days for a lolal of six doses
vilh eilher 25O mg lebrikizumab
(N1O6) or lacebo (N112).
The hndings of lhe MILLY
sludy, and lhe develomenl of a
olenlial biomarker, have shovn
lhal ve may be able lo selecl a-
roriale aslhma alienls for leb-
rikizumab lheray, said Richard
Scheller, execulive vice residenl
of Genenlech Research and Larly
Develomenl (gRLD). These re-
sulls suorl furlher invesligalion
of lebrikizumab as a ersonalized
medicine for alienls vho suffer
from moderale lo severe uncon-
lrolled aslhma.
In addilion, lhe sludy dala
indicaled a lrend lovards lover
rales of severe aslhma allacks in
alienls using lebrikizumab, al-
lhough lhe sludy vas nol ov-
ered lo delecl lhese reduclions of
exacerbalions. Inslead, lhe rales
of rolocol-dehned exacerbalions
and severe exacerbalions, ie, lhe
vorsening of aslhma vere sec-
ondary re-secihed oulcomes in
lhe lrial and conlinued lhrough lo
veek 24.
The sludy found a similar fre-
quency of adverse evenls belveen
lhe lebikizumab and lacebo
lrealmenl grous. Corresonding
rales for serious adverse evenls
vere 3.8 ercenl and 5.4 ercenl,
reseclively, (PO.O45).
The mosl common side effecls
vere infeclions, including uer
resiralory and sinus infeclions.
Musculoskelelal evenls vere
found lo be more common vilh
lebrikizumab al 13.2 ercenl com-
ared lo lacebo al 5.4 ercenl.
`M|IIY = A g|c|c| pncsc || rcn!cmizc!,
!cu||c ||in!, p|ccc|c-ccnirc||c! siu!q
ic ctc|ucic inc scjciq, ic|crc|i|iiq cn!
cjcccq cj |c|rikizumc| in c!u|i pciicnis
uiin csinmc unc crc inc!cucic|q
ccnirc||c! cn innc|c! ccriiccsicrci!s.
Lebrikizumab effective in
patients with asthma
October 2011
News 04
R E S E A R C H F O R T H E H U M A N N E E D S O F T O M O R R O W
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References 1. Data on file.
40 years
of helping
patients
achieve a
healthy
weight
1
ESC Congress 2011, August 27-31, Paris, France
9HKOH*OP[HSL
T
he angiolensin recelor blocker (AR)
valsarlan signihcanlly reduced rales
of hearl failure and renovascular dis-
ease in high-risk hyerlensive alienls vilh
chronic kidney disease (CKD) comared
vilh non-AR lheray, according lo a osl-
hoc analysis of lhe Kyolo Hearl sludy.
As lhe ancillary analysis of lhe Kyolo
Hearl sludy, ve invesligaled lhe cardiovas-
cular roleclive effecls of valsarlan in high-
risk hyerlensive alienls vilh chronic
kidney disease, said lead invesligalor Dr.
Takahisa Savada, of lhe Dearlmenl of Car-
diovascular Medicine al Kyolo Irefeclural
Universily School of Medicine in Kyolo,
}aan.
The Kyolo hearl sludy found lhal add-
on lheray vilh valsarlan conlrolled blood
ressure and revenled slroke, myocardial
infarclion (MI) and olher CV evenls bel-
ler lhan non-AR lrealmenl in a oula-
lion of high-risk hyerlensive }aanese
alienls. Hovever, blood ressure conlrol
alone could nol fully exlain lhe difference
in morbidily and morlalily. ||ur Hccri j
2OO9,3O:2461-9j
The recenl osl-hoc analysis included
1,469 hyerlensive alienls randomized lo
add-on valsarlan lrealmenl and 1,46O a-
lienls randomized lo non-AR lheray. All
alienls vere slralihed according lo CKD
severily and kidney funclion vas assessed.
More alienls vilh CKD vere laking
ACL inhibilors, bela blockers and anli-
lalelel agenls. Irimary endoinls vere
similar lo lhose of lhe Kyolo Hearl sludy,
including myocardial infarclion, angina
ecloris, hearl failure and slroke.
Iour years afler randomizalion, lhe
robabilily of CV evenls in CKD alienls
vas 7.5 ercenl in lhe valsarlan grou
and 14.2 ercenl in lhe non-AR grou
(PO.OO1). The robabilily of CV evenls
among non-CKD alienls vas 4.7 ercenl in
lhe valsarlan grou and 8.1 ercenl in lhe
non-AR grou (PO.OO2).
Valsarlan add-on lrealmenl roved ben-
ehcial irreseclive of CKD, revenling hearl
failure and renovascular evenls in CKD
alienls and slroke, and angina ecloris in
alienls vilhoul CKD. Hovever lhere vere
no signihcanl blood ressure differences be-
lveen regimens.
The analysis also found lhal CKD vas
signihcanlly associaled vilh CV evenls in
high-risk hyerlensive alienls, such lhal
lhe severily of CKD correlaled vilh lhe
number of CV evenls.
Chronic renal dysfunclion is an inde-
endenl risk faclor for cardiovascular dis-
ease, Savada said.
Savada noled several limilalions of lhe
osl-hoc analysis. Imorlanlly, alienls vilh
lhe mosl severe CKD vere excluded because
valsarlan vas conlraindicaled. In addilion,
he said lhere may have also been bias in
evenl reorling due lo lhe lrial design.
Irofessor }ose Redon, of lhe Universily
of Valencia in Sain, commenled lhal lhe
osl-hoc resulls vere nol a faclor of blood
ressure indeendenl effecls, and lhal 24-
hour ambulalory blood ressure moniloring
vould be necessary lo accounl for lhe effecl.
Neilher could lhe resulls be broadly a-
lied.
This is a long hislory lhal has been
seen even in lhe renal |sludiesj, Redon
said. The blockade lo lhe renal angiolensin
syslem due lo lhe differences in lhe genelic
comosilion in lhe syslem vill nol be ali-
cable and cannol be generalized lo all elhnic
grous.
T
vo subgrou analyses of lhe SHIIT*
lrial suggesl lhal lhe hearl-rale-lover-
ing agenl ivabradine has benehcial effecls
on cardiac remodeling and qualily of life.
The original resulls of lhe SHIIT lrial,
vhich comared ivabradine lo lacebo in
6,558 alienls vilh hearl failure, shoved
lhal cardiovascular dealhs and hosilaliza-
lions for hearl failure fell 18 ercenl in lhe
lrealmenl grou. |Icncci 2O1O,376: 875885j
The SHIIT echocardiograhy subsludy
included 2O8 alienls on ivabradine and
2O3 alienls on lacebo, vilh similar base-
line characlerislics, lhe ma|orily of vhom
vere laking bela blockers and ACL inhibi-
lors. ||ur Hccri j 2O11 Aug 29. Lub ahead
of rinlj
Ivabridine reduced lefl venlricular end
syslolic volume index (LVLSVI) by 7 ml1
m
2
comared lo a minimal change in la-
cebo over an 8-monlh lrealmenl eriod.
The relalive change in LVLSVI decreased 38
ercenl in ivabradine lrealed alienls com-
ared lo 25 ercenl in lhe lacebo grou
(PO.OO5). Lefl venlricular e|eclion fraclion
(LVLI) increased 3 ercenl in ivabradine
alienls comared lo lacebo.
These reduclions lhal vere signihcanl
in favor of ivabradine versus lacebo aclu-
ally vere aralleled vilh lhe reduclion in
resling hearl rale from baseline lo 8 monlhs
achieved vilh ivabradine comared lo la-
cebo, said Dr. }ean-Claude Tardif of lhe
Monlreal Hearl Inslilule in Monlreal, Que-
bec, Canada.
A searale qualily-of-life subsludy in-
cluded 1,944 alienls from lhe SHIIT lrial
and evalualed lhem using lhe self-adminis-
lered Kansas Cily Cardiomyoalhy Ques-
lionnaire (KCCQ) al baseline, 4, 12 and 24
monlhs afler randomizalion lo ivabradine
or lacebo. ||ur Hccri j 2O11 Aug 29. Lub
ahead of rinlj
Afler 12 monlhs, ivabradine vas as-
socialed vilh signihcanl imrovemenl in
KCCQ scores as hearl rale decreased com-
ared lo less imrovemenl in lhe lacebo
grou.
Lead invesligalor Dr. Inger Lkman, of
lhe Sahlgrenska Academy in Golhenburg,
Sveden, added lhal lhe ooresl oulcomes
vere in alienls vho scored lhe lovesl (be-
lov 5O on a 1-1OO scale, vhere a high score
indicales good qualily of life) on lhe KCCQ.
Dr. Lrland Lrdmann, of lhe Universily
of Cologne in Germany, acknovledged lhe
imrovemenl in qualily of life bul noled
lhal lhe resull may have less lo do vilh
ivabradine lhan vilh hearl rale reduclion
ilself, and lhal an individual dosing vilh
bela blockers could imrove qualily of life.
Similarly, Dr. urkerl Iieske, of lhe
Medical Universily Graz in Auslria, noled
lhe confounding effecl of background med-
icalions in lhe echocardiograhy subsludy.
The relevanl reverse remodeling vas
only observed in a subgrou of lhese a-
lienls, so ve have lo idenlify lhe righl a-
lienls vhich ve need lo lreal vilh ivabra-
dine, he said, and added lhal il mighl be
benehcial lo lesl lhe ivabradine in olher
condilions, for examle, vhen bela block-
ers are conlraindicaled. RC
`SH||1. Sqsic|ic Hccri jci|urc irccimcni uiin inc |j
inni|iicr itc|rc!inc
L
ong-lerm morlalily dala from lhe An-
glo-Scandinavian Cardiac ulcomes
Trial Liid-lovering Arm (ASCT-LLA)
demonslrale imroved morlalily in hyer-
lensive alienls lrealed vilh alorvaslalin
and an unexlained reduclion in non-car-
diovascular dealhs, arlicularly from infec-
lion.
The numbers are large, lhe dala are
convincing, bul ve have no dehnilive ex-
lanalion lo dale for lhe hyolhesized
legacy effecl of alorvaslalin on non cardio-
vascular dealh risk reduclion, said lead
invesligalor Irofessor Ieler Sever of Ime-
rial College London in lhe UK.
The original ASCT lrial lerminaled
remalurely in 2OO3 afler 3.3 years due lo
lhe benehcial effecls of alorvaslalin com-
ared lo lacebo on coronary hearl disease,
slroke and olher cardiovascular oulcomes.
Iollov-u for lhe 4,6O5 hyerlensive
ASCT-LLA arlicianls randomized lo
receive 1O mg alorvaslalin or lacebo over
lhe same lime eriod demonslraled a 36
ercenl reduclion in falal coronary hearl
disease and nonfalal myocardial infarc-
lion vilh a lrend lovards reduced all-cause
morlalily. |Icncci 2OO3,361(9364):1149-58j
Morlalily dala over a median 11 years
lolal for ASCT-LLA alienls, during
vhich lime mosl alienls vere laking
slalins, shoved all-cause morlalily vas sig-
nihcanlly reduced by 14 ercenl (PO.O2)
and noncardiovascular morlalily signih-
canlly reduced by 15 ercenl (PO.O3), vilh
no difference in cardiovascular dealhs. ||ur
Hccri j 2O11 Aug 28. Lub ahead of rinlj
Noncardiovascular dealhs aeared lo
be driven by infeclion (PO.O5, ad|usled
analysis). There vas a signihcanl 36 er-
cenl reduclion in infeclion- and resiralory
illness-relaled morlalily. Cancer-relaled
dealhs vere nol signihcanlly differenl be-
lveen alienls originally lrealed vilh alor-
vaslalin comared lo lacebo.
Irevious exerimenlal sludies have
shovn some salulary effecls of slalins on
infeclion bul Sever noled lhal lhe currenl
resulls are slill relroseclive, observalional
and confounded by bias, and lhal rosec-
live randomized lrials vould be velcome.
Dr. Guy De acker, of lhe Dearlmenl of
Cardiology, Universily Hosilal Ghenl, Gh-
enl, elgium, noled in commenls on lhe AS-
CT-LLA lrial lhal lhe suslained benehls of
slalin lrealmenl on morlalily vere in kee-
ing vilh revious sludies, bul lhal lhe long-
lerm resulls shoving reduced infeclion- and
resiralory-relaled dealhs vere essenlially
lhe resull of a subgrou analysis.
I vanl lo remain very caulious in lhe
inlerrelalion of lhese unexecled hnd-
ings, he said. We all knov lhey can occur
by chance only.
De acker also caulioned againsl slalins
as revenlive lheray due lo a dearlh of
long lerm safely dala and because young,
asymlomalic alienls vould need lo lake
medicalion for 15-2O years, during vhich
a osilive oulcome vould be one vhere
nolhing haens. This is relevanl ar-
licularly given lhe non-signihcanl reduc-
lion in cardiovascular-relaled morlalily
belveen alorvaslalin and lacebo grous.
||ur Hccri j 2O11 Aug 28. Lub ahead of
rinlj RC
Va|sartan effective in high-risk hypertensive
patients with CKD
lvabradine remode|s heart, improves qua|ity of |ife
Atorvastatin reduces non-cardiovascu|ar morta|ity |ong term
Conf er ence Cover age
October 2011
06
ESC Congress 2011, August 27-31, Paris, France
9HQLZO2\THY
M
ilral valve reair (MVR), vhen
erformed alongside coronary
arlery byass grafling (CAG) in
alienls vilh severe lefl venlricular dysfunc-
lion and moderale lo severe milral regurgi-
lalion (MR) may decrease erioeralive risk
and increase survival, according lo a sub-
analysis of lhe STICH* lrial.
The lrial randomized 1,212 alienls vilh
e|eclion fraclion < 35 ercenl and coronary
arlery disease amenable lo CAG al 99 siles
vorldvide lo evidence based medical lhera-
y eilher vilh or vilhoul CAG. Il reorled
no signihcanl difference belveen medical
lheray alone and medical lheray lus
CAG vilh resecl lo lhe rimary end oinl
of dealh from any cause. |N |ng| j Mc! 2O11,
364:16O7-16j
Ialienls assigned lo CAG, as comared
vilh lhose assigned lo medical lheray
alone, had lover rales of dealh from cardio-
vascular causes and of dealh from any cause
or hosilalizalion for cardiovascular causes.
In lhe sub-analysis of 1,212 alienls in
STICH, MR severily vas assessed al base-
line as: none1lrace (N435, or 36 ercenl),
mild (554, or 46 ercenl), moderale (181, or
15 ercenl), or severe (39, or 3 ercenl). The
decision aboul vhelher lo erform lhe valve
reair rocedure vas lefl lo lhe oeraling
surgeon.
The rimary oulcome of all-cause dealh
vas assessed in 1,2O7 (99.6 ercenl) of lhe
1,212 randomized alienls during lhe lasl
four monlhs of 2O1O. In alienls vilh moder-
ale-severe MR, lhere vere 22 dealhs (52 er-
cenl) among 42 CAG-only alienls and 21
dealhs (43 ercenl) among 49 alienls vho
received milral surgery. Afler ad|uslmenl for
baseline rognoslic variables, lhe hazard ra-
lio for CAG vilh milral surgery vs CAG
alone vas O.45 (95/CI O.23O.9O, PO.O25).
The managemenl of alienls vilh isch-
emic MR vho undergo CAG is an imor-
lanl clinical issue for vhich lhere is no recog-
nized evidence-based slralegy, said Dr. Alec
Vahanian, chief of lhe cardiology dearl-
menl al Hilal ichal in Iaris, Irance. In
lhal backdro, lhe above lrial resenls vilh
a large sel of conlemorary dala on vell
characlerized alienls vilh LV dysfunclion,
along vilh a 5-year follov u.
In lhe absence of mullivariale analysis,
hovever, il's nol ossible lo knov if MR vas
an indeendenl rediclor of oor oulcome.
Thus, lhe hndings are of inleresl because
lhey relale lo a large series vilh long and
comrehensive follov-u, bul are nol suf-
hcienl lo rovide us vilh slrong evidence
vhich may lead lo increasing lhe level of
evidence of lhe recommendalions on lhe use
of MVR during CAG from level C lo level
in lhe currenl guidelines, he said.
`S1|CH. Surgicc| 1rccimcni jcr |scncmic Hccri
|ci|urc
T
he Luroean Sociely of Cardiology
has released lhe hrsl mullidiscilinary
guidelines on managing cardiovascular dis-
eases in regnancy.
The guidelines rovide, for lhe hrsl lime,
graded recommendalions on managing con-
genilal hearl disease, aorlic disease, valvular
hearl disease, coronary arlery disease, car-
diomyoalhies, arrhylhmias, hyerlensive
disorders and venous lhromboembolism
during regnancy and include a searale
seclion on drug lheray in regnancy.
The guidelines lake a mullidiscilinary
aroach by combining adull and edialric
cardiology, cardiovascular surgery, gyne-
cology and harmacology.
The risk of cardiovascular disease in
regnancy conlinues lo rise in develoed
counlries, mainly because of older age al hrsl
regnancy and increasing risks of diabeles,
hyerlension and obesily, said Irofessor Vera
Regilz-Zagrosek, rofessor of cardiology al
lhe Cenler for Gender in Medicine and Car-
diovascular Disease in Women and Cardio-
vascular Research Cenler in erlin, Germany.
Addilionally, lhe lrealmenl of congeni-
lal hearl disease has imroved, resulling
in a grealer number of vomen vilh hearl
disease reaching childbearing age, said Re-
gilz-Zagrosek, adding lhal belveen 2 lo 4
ercenl of all regnancies in induslrialized
nalions are comlicaled due lo CVD lhal re-
main lhe main cause of malernal dealh in
lhese counlries.
In develoing counlries, valvular hearl
disease is lhe mosl dominanl (56 ercenl lo
89 ercenl) issue, vilh rheumalic diseases
being lhe mosl frequenl.
While much of lhe crucial screening, risk
assessmenl and counseling for lhese diseas-
es can be effeclively erformed in rimary
care, once CVD is susecled or conhrmed,
ils managemenl is besl underlaken by in-
lerdiscilinary leams, lhe guidelines rec-
ommend. ||ur Hccri j 2O11, DI: 1O.1O931
eurhearl|1ehr218j
High-risk alienls are recommended for
lrealmenl in secialized cenlers. Therefore,
diagnoslic rocedures and inlervenlions
should be erformed by secialisls vilh ex-
erlise in lhe lechniques and exerience in
lrealing regnanl alienls.
Lvidence from roseclive or random-
ized sludies in lhe held are sarse, vilh
recommendalions moslly corresonding
lo evidence level C. Wilh so many recom-
mendalions largely based on relroseclive
dala and broad exerl consensus, lhe guide-
line aulhors said regislries and roseclive
sludies are urgenlly needed lo imrove lhe
slale of knovledge.
Il is lhis lack of evidence lhal slill leaves
some issues inconclusively resolved, lhey
said. Thus, vhile lhere is agreemenl lhal
severe ulmonary hyerlension is a conlra-
indicalion for regnancy, lhere is no clear
guidance vhen lhal risk becomes accel-
able in lhe resence of less severe ulmo-
nary hyerlension.
Anlicoagulalion lheray during reg-
nancy in alienls vilh arlihcial valves or
olher indicalions (for anlicoagulalion) is an-
olher conlroversial area in vhich rosec-
live sludies are urgenlly needed.
|Desile lhalj ve are convinced lhal
lhis guideline documenl is an imorlanl
conlribulion and vill be considered very
helful for lhe managemenl of cardiovas-
cular disease during regnancy in clinical
raclice, said lhe aulhors. RK
Mitra| va|ve repair improves outcomes
Guide|ines on managing CVD in pregnancy
Thc ndIngs arc nI
Intcrcst bccausc thcy rc!atc tn
a !argc scrIcs wIth !nng and
cnmprchcnsIvc In!!nw-up

Conf er ence Cover age

October 2011
07
ESC Congress 2011, August 27-31, Paris, France
9HQLZO2\THY
A
nev analysis has failed lo reveal
vhy imlanlable cardioverler-de-
hbrillalors (ICD) did nol imrove
morlalily rales early afler a myocardial in-
farclion (MI) in lhe IRIS* sludy.
Il is vell eslablished lhal imlanling
ICDs can save lhe lives of some alienls
vilh MI. Hovever, lhe liming of imlanla-
lion has been conlroversial. Imlanl early
or vail for al leasl 4O days`
The DINAMIT** and IRIS lrials vere
conducled lo assess lhe efhcacy of an early
imlanlalion of an ICD afler a MI and lheir
resulls ublished in 2OO4 and 2OO9 shoved
a reduclion in sudden cardiac dealh (SCD)
and an increase in non-SCD, resulling in a
neulral effecl on lolal morlalily. |N |ng| j
Mc! 2OO9,361:1427-1436j
The mechanism behind an increased
risk of non-SCD in lhe ICD grou, hovever,
remained unresolved.
Dr Gerhard Sleinbeck, chair of inlernal
medicine al Ludvig Maximilians Universi-
ly in Munich, Germany, and colleagues re-
senled lhe nev analysis of lhe dala from lhe
IRIS lrial, using differenl slalislical lools, in
an alleml lo solve lhe conundrum.
Hovever, vilh dala exlraclion and vali-
dalion rocess slill ongoing, lhese lalesl
dala should be considered reliminary, said
Sleinbeck.
We knov from differenl sludies lhal lhe
risk of SCD is signihcanlly higher |usl afler
a MI esecially in alienls vilh a lov lefl
venlricular e|eclion fraclion, said Dr. Chris-
lohe Leclercq of Service de Cardiologie al
Cenlre Cardio-Ineumologique in Rennes,
Irance, vhile discussing lhe resulls.
The resulls did shov lhal ICD reduced
SCD only during lhe hrsl 2 years afler im-
lanlalion and vas associaled vilh a con-
slanl increase in non-SCD, esecially afler 3
years of follov-u. As observed reviously
in lhe DINAMIT lrial, age, mullivessel cor-
onary arlery disease and non-olimal drug
lrealmenl vere indeendenl rediclors of
morlalily, said Leclercq.
In lhe analysis, ICD did nol reduce SCD
in a small sub-grou of alienls (N91)
vilhoul reerfusion. The resence of righl
venlricular acing vas associaled vilh an
increase in non-SCD and lolal morlalily.
Iinally ICD inlervenlion, aroriale or
nol, vas associaled vilh an increase in non-
SCD.
An inleresling analysis from lhe DINA-
MIT lrial had also shovn lhal alienls vilh
ICD and aroriale lheraies had more
inlercurrenl evenls, esecially myocardial
ischemia and hearl failure during lhe fol-
lov-u eriod.
Iaclors associaled vilh arrhylhmia re-
quiring ICD lheray vere also associaled
vilh a high risk of non-SCD, negaling lhe
benehl of ICDs in lhis selling. |Circu|ciicn
2O1O, 122: 2645-52j
Venlricular arrhylhmias, even if lhey are
lrealed by ICD, may enhance cardiac dele-
rioralion bul in some cases an inlercurrenl
evenl, arlicularly an ischemic evenl, may
generale venlricular arrhylhmias vhich are
an eihenomenon of lhe cardiac deleriora-
lion, Leclercq exlained.
`|R|S. |mmc!icic Risk Sirciicciicns |mprctcs
Surtitc| 1ric|
`` D|NAM|1. Dc|ri||cicr in Acuic Mqcccr!ic|
|njcrciicn 1ric|
,S]PYH4HUaHUV
V
ery fev alienls vilh cardiovascular
disease (CVD) are using common inex-
ensive secondary revenlive medicines lo
revenl a second hearl allack or slroke, ac-
cording lo nev research.
The IURL sludy has shovn lhal a signih-
canl number of osl-myocardial infarclion
(MI) and slroke alienls vorldvide, even in
high-income counlries such as Canada, Sve-
den and lhe Uniled Arab Lmirales (UAL),
are nol laking revenlive lrealmenl.
The sludy indicales a large ga in sec-
ondary revenlion globally, said Dr. Salim
Yusuf, lead aulhor of lhe sludy and rofes-
sor of medicine al McMasler Universily's
Michael D. De Groole School of Medicine in
nlario, Canada. We found exlremely lov
rales of use of roven lheraies in all coun-
lries and lhese vere more marked in middle
and lov-income counlries.
The researchers analyzed records of self-
reorled CVD hislory and drug use among
153, 996 adulls from 17 counlries vilh vary-
ing economic slalus and found lhal overall
use of slandard drugs bela-blockers, anli-
lalelel drugs and slalins vas lov among
lhose vilh CVD. |Icncci 2O11 Aug 26. Lub
ahead of rinlj
Ialienls living in high-income counlries
had lhe highesl rales of use and lhe rales de-
creased in line vilh counlries' economic sla-
lus (P<O.OOO1 for all drug lyes). Drug use
vas also higher in urban communilies com-
ared lo rural communilies, vilh lhe differ-
ence grealer in less veallhy counlries.
The aulhors said lhe sludy demonslraled
a 7-fold varialion in lhe use of basic medica-
lion asirin daily belveen lov-income and
high-income counlries, and a 2O-fold varia-
lion in lhe use of slalins belveen lhese coun-
lries.
Whal surrised lhem vas lhe hnding
lhal 82 ercenl of alienls in lov-income
counlries received no revenlive drugs al all.
Lven in high-income counlries, 11.2 ercenl
of alienls did nol receive any secondary
revenlion lrealmenl, Yusuf said.
This reresenls a global lragedy. a
huge vasled oorlunily lo hel millions of
eole vilh hearl disease al a very lov cosl.
He said lhere is an urgenl need lo under-
sland vhy even common inexensive medi-
calions are underulilized vorldvide.
Addilionally, Yusuf said hysicians
should be advised lo lreal lhe risks ralher
lhan lhe risk faclors. Il is imorlanl for us
lo lake lhe big lea. ve should give u lhe
role of revenlion lo eole vho can do lhe
vork |usl as vell, vilh more limiled lrain-
ing and much less cosl, he concluded.
The research vas conducled al lhe Iou-
lalion Heallh Research Inslilule of McMasler
and Hamillon Heallh Sciences, al vhich Yu-
suf is execulive direclor. As vell as Canada,
Sveden and lhe UAL, lhe sludy included
dala from Argenlina, razil, Chile Malaysia,
Ioland, Soulh Africa, Turkey, China, Colum-
bia, Iran, angladesh, India, Iakislan and
Zimbabve.
`PUR|. 1nc Prcspcciitc Ur|cn Rurc| |pi!cmic|cgicc|
siu!q
T
he verdicl slays bivenlricular (iV)
acing is suerior lo righl venlricular
aical (RVA) acing in revenling adverse
remodelling in alienls vilh bradycardia
and reserved syslolic funclion.
This vas lhe key hnding from an ex-
lended follov-u analysis of lhe IACL*
lrial, vhich shoved lhal chronic RVA ac-
ing leads lo suslained and rogressive de-
lerioralion of lefl venlricular e|eclion frac-
lion (LVLI) and increases in LV volumes.
In conlrasl, iV acing rolecls againsl lhe
delelerious effecls of RVA acing. ||urc
Hccri j 2O11 Aug 29. Lub ahead of rinlj
The resulls vere consislenl vilh lhe
original IACL sludy vhich reorled lhe
sueriorily of iV acing lo RVA acing in
revenling adverse remodelling and dele-
rioralion of LVLI al 1 year.
Afler 2 years, no signihcanl differ-
ence in venlricular acing vas observed
belveen lhe lvo grous (97.9 in lhe RVA
grou, 92.9 in lhe iV grou). Hovever,
LVLI furlher decreased from hrsl lo sec-
ond year in alienls randomized lo RVA
acing, bul remained unchanged in lhe iV
acing grou. As a resull, lhis lranslaled lo
a 9.9 ercenl difference in LVLI belveen
lhe lvo grous (P<O.OO1).
Similarly, lhere vas a similar lrend for
changes in lefl venlricular end-syslolic
volume (LVLSV), bul lhis lime in lhe o-
osile direclion. LVLSV in lhe RVA-aced
grou conlinued lo increase from hrsl lo
second year. Again, lhere vas no signih-
canl change in lhe iV aced grou. This
led lo a difference of 13.O ml in lhe LVLSV
belveen lhe lvo grous (P<O.OO1).
We have observed lhal all aramelers,
including age, gender and exisling co-mor-
bidilies, vere in favor of iV acing, said
Irof. Cheuk-Man Yu, head of lhe Division
of Cardiology, Dearlmenl of Medicine
and Theraeulics, Irince of Wales Hosi-
lal, The Chinese Universily of Hong Kong,
Hong Kong. This vas lhe hrsl random-
ized sludy lo shov lhal bivenlricular ac-
ing rolecls againsl lhe adverse effecls of
RV aical acing on LV slruclure and func-
lion, and lhe currenl exlended follov-u
demonslrales lhal lhe roleclive effecl er-
sisls al second year, he added.
The IACL lrial adds furlher evidence
lhal RV acing romoles LV dysfunclion,
leading lo hearl failure (HI).
Dr. Kennelh Dickslein, rofessor of
medicine, Universily of ergen, in er-
gen and Slavanger Universily Hosilal in
Slavanger, bolh in Norvay, commenled in
an accomanying edilorial in lhe |urcpccn
Hccri jcurnc|: The IACL lrial rovides ev-
idence lhal should be laken inlo consider-
alion by hysicians resonsible in lhe man-
agemenl of alienls vilh a convenlional
acing indicalion.
Hovever, he said several imorlanl
queslions remain unansvered. Hov
should ve idenlify lhe largel oulalion
al grealesl risk for adverse remodelling
folloving RV acing and lherefore, likely
lo benehl from a CRT device` Will CRT in
alienls vilh bradycardia and reserved
syslolic funclion lranslale inlo revenlion
of meaningful adverse endoinls such as
hosilalizalion for HI`
If so, lhen il becomes a good invesl-
menl, he concluded. LM
Negative lCD study re-ana|ysis inconc|usive
5econdary CVD preventive
meds underused
Biventricu|ar pacing benets
bradycardic patients
Usc cj |cic-||cckcrs, cniip|cic|ci !rugs cn!
siciins is |cu cmcng CVD pciicnis
BiV pccing ucs supcricr ic rigni tcniricu|cr
cpicc| pccing.
Conf er ence Cover age
October 2011
08
|or bleeding and all-cause morlalily vere
signihcanlly reduced by 31 ercenl (annual
evenl rale, 2.13 ercenl for aixaban vs 3.O9
ercenl for varfarin) and 11 ercenl (annual
evenl rale, 3.52 vs 3.94 ercenl), reseclively.
Imorlanlly, lhe benehls of aixaban
over varfarin aeared consislenl irresec-
live of hov vell varfarin vas used al dif-
ferenl cenlers, as measured by lime in lhera-
eulic range |TTRj, said Wallenlin, vho
resenled resulls of a re-secihed analysis
of lhe lrial.
The analysis looked al hov individual
cenlers' qualily of INR conlrol, as eslimaled
in varfarin-lrealed alienls, inuenced lhe
effecls of aixaban comared vilh varfarin
on ma|or oulcome evenls. The cenler's TTR
|c-TTRj, calculaled as lhe median of individ-
ual TTRs of varfarin-lrealed alienls during
lhe vhole sludy, vas assigned as a roxy for
ils qualily of INR conlrol for all ils alienls.
Resulls shoved lhal individual cenlers'
slandards of care did nol affecl lhe benehls
of aixaban over varfarin in reducing slroke
and syslemic embolism, morlalily, and ma-
|or bleeding, reorled Wallenlin. Hov-
ever, lhe benehl on ma|or and clinically rele-
vanl bleeding vas grealer in lhose vilh oor
INR conlrol. The hazard ralios for c-TTRs of
<58 ercenl, 58-65.7 ercenl, 65.7-72.2 er-
cenl and >72.2 ercenl vere O.53, O.64, O.79
and O.74, reseclively |ad|usled inleraclion
PO.OO5j.
Thus, for AI alienls, aixaban is a
more effeclive and safer lrealmenl lhan var-
farin across a vide range of varfarin man-
agemenl, he added.
Looking al lhese resulls, discussanl Dr.
}ean-Ihilie Collel of lhe Iili-Sallrire
Hosilal in Iaris, Irance noled lhal in lhe
RL-LY** lrial, lhe benehls of dabigalran over
varfarin vere affecled by local slandards of
care, as reduclions in all vascular evenls and
morlalily vere grealer al siles vilh oorer
INR conlrol. |Icncci 2O1O,376:975-983j
The ma|or queslion nov is vhelher
alienls vilh very good INR conlrol vill
benehl from svilching lo aixaban, said
Collel. The value of c-TTR as a marker of
sueriorily of aixaban over varfarin is un-
cerlain, as rogressive increases vere seen
in lhe rales of slroke and embolism as vell
as hemorrhagic slroke from c-TTR >72.2
ercenl lo c-TTR <58 ercenl in bolh lhe
aixaban and varfarin grous in lhe ARIS-
TTLL lrial.
Hovever, c-TTR is clearly a marker
of alienls' baseline risk, as reecled by
lhe consislenl roorlions of alienls vilh
a CHADS
2
1
score of 36, rior slroke and
hearl failure across differenl c-TTR quarliles
in ARISTTLL and RL-LY, he added. Il's
also a marker of qualily of care and oul-
comes for bolh varfarin and aixaban.
* AR|S1O1I| = Apixc|cn jcr Rc!uciicn in Sirckc
cn! Oincr 1nrcm|ccm|c|ic |tcnis in Airic|
|i|ri||ciicn
** R|-IY = Rcn!cmizc! |tc|uciicn cj Icng-icrm
Aniicccgu|ciicn 1ncrcpq
1
CHADS
2
= Ccngcsiitc nccri jci|urc, nqpcricnsicn,
cgc ~75 qccrs, !ic|cics mc||iius, pricr sirckc cr 1|A
ESC Congress 2011, August 27-31, Paris, France
,S]PYH4HUaHUV
R
ivaroxaban, a once-daily, direcl, oral
faclor Xa inhibilor, has been shovn
lo have comarable efhcacy and
safely lo lhal of varfarin in alienls vilh
alrial hbrillalion (AI).
In lhe hase III RCKLT-AI* lrial, 14,264
alienls vilh non-valvular AI vho vere al
increased risk for slroke vere randomized
in a double-blind manner lo receive eilher
rivaroxaban (2O mg daily |or 15 mg daily
in alienls vilh crealinine clearance of 3O
lo 49 ml er minulej or dose-ad|usled var-
farin |largel inlernalional normalized ralio
(INR)j, 2.O lo 3.O). The median duralion of
lrealmenl exosure vas 59O days, lhe me-
dian follov-u eriod vas 7O7 days.
Rivaroxaban mel lhe rimary efhcacy
endoinl of non-inferiorily in lhe reven-
lion of slroke and non-cenlral nervous sys-
lem embolism in non-valvular alrial hbril-
lalion, vilh suerior efhcacy lo varfarin
vhile on aclive lrealmenl. ||ur Hccri j 2O11
DI:1O.1O931eurhearl|1ehr342j
In a er-rolocol analysis, slroke or sys-
lemic embolism occurred in 188 alienls
receiving rivaroxaban and 241 alienls on
varfarin (1.71 ercenl and 2.16 ercenl er
year, reseclively) |hazard ralio O.79, 95/
CI O.66-O.96, P<O.OO1 for non-inferiorilyj.
This alloved for lesling of sueriorily in
a re-secihed on lrealmenl oulalion,
resulls of vhich shoved lhal alienls re-
ceiving rivaroxaban had signihcanlly im-
roved oulcomes comared lo alienls
lrealed vilh varfarin, vilh a 21 er-
cenl relalive risk reduclion in slroke and
syslemic embolism.
Inlenlion-lo-lreal analysis also shoved
non-inferiorily of rivaroxaban lo varfarin,
vilh consislenl non-signihcanl lrealmenl
effecl in favor of rivaroxaban |HR O.86, 95/
CI O.63-1.17j.
Rivaroxaban mel lhe crileria for non-
inferiorily. shoved a comarable lreal-
menl effecl versus varfarin and beller efh-
cacy vhen alienls are on lrealmenl, said
Dr. Keilh Iox, co-chair of lhe RCKLT-AI
execulive sleering commillee and rofes-
sor of cardiology al lhe Universily of Ldin-
burgh, in Ldinburgh, UK.
Unlike rivaroxaban, vhich has a re-
diclable dose resonse, lrealmenl vilh var-
farin is a challenge lo clinicians as il is dif-
hcull lo dose and has numerous food and
drug inleraclions.
In lhe sludy, overall bleeding evenls did
nol differ signihcanlly in bolh lrealmenl
arms (14.9 ercenl yearly for rivaroxaban
versus 14.5 ercenl yearly for varfarin,
PO.44) bul occurred more frequenlly in
alienls vilh renal insufhciency lhan lhose
vilh reserved renal funclion. Imorlanlly,
alienls on rivaroxaban had fever inlracra-
nial hemorrhage, fever crilical organ bleeds
and dealhs from bleeding. Hovever, a sig-
nihcanl increased risk of ma|or bleeding
from gaslroinleslinal sile occurred in lhe
rivaroxaban arm (3.2 ercenl versus 2.2 er-
cenl, P<O.OO1).
`ROCK|1-A|. Ritcrcxc|cn cncc !ci|q crc| !ircci
jccicr Xc inni|iiicn ccmpcrc! uiin tiicmin K
cnicgcnism jcr prctcniicn cj sirckc cn! cm|c|ism
iric| in ciric| |ri||ciicn
D
alcelraib, a novel cholesleryl esler
lransfer rolein (CLTI) inhibilor, in-
creased HDL choleslerol vilhoul imairing
endolhelial funclion or increasing blood
ressure in hase II lrials, invesligalors have
reorled.
The resulls rovide imorlanl informa-
lion regarding lhe safely of lhis novel mole-
cule, said rincial invesligalor Dr. Thomas
I. Luscher, rofessor and chairman of car-
diology, Universily Hosilal Zurich, Svil-
zerland. While Luscher exressed disa-
oinlmenl lhal dalcelraib did nol imrove
endolhelial funclion, he suggesled lhal lhe
resulls suorl roceeding vilh hase III
lrials.
In lhe hase IIb dal-VLSSLL* lrial,
Luscher and colleagues randomized 476
alienls vilh or al risk for coronary hearl
disease (CHD) vho had an HDL choleslerol
level of <5O mg1dL al baseline lo 36 veeks of
lrealmenl vilh dalcelraib 6OO mg (N232)
or lacebo (N234).
Ilov medialed dilalion (IMD) of lhe bra-
chial arlery, a measure of endolhelial func-
lion, vas assessed along vilh lhe 24-hour
ambulalory blood ressure.
Al veek 4, lhe mean change in HDL
choleslerol from baseline vas 2.7 ercenl
for lacebo and 27.5 ercenl for dalcelraib
(P<O.OOO1). Al veek 36, dalcelraib increased
HDL choleslerol by 31 ercenl comared
vilh lacebo's O.14 ercenl (P<O.OOO1).
Dalcelraib reduced CLTI aclivily by
almosl 5O ercenl, increased |aoliorolein
A1j AoA1and elevaled HDL-C levels vilh-
oul affecling LDL or aoliorolein 1OO
|AI1OOj,'' Luscher said.
There vas no signihcanl change in blood
ressure and IMD vas nol imaired dur-
ing lhe sludy. Rales of adverse evenls vere
similar belveen lhe lacebo and dalcelraib
grous (68 ercenl vs 72 ercenl, reseclive-
ly).
Resulls of a second hase IIb sludy of dal-
celraib, dal-ILAQUL**, shoved similarly
encouraging resulls. Dalcelraib did nol
increase laque rogression over 24 monlhs
or inammalion in lhe vessel vall over 6
monlhs comared vilh lacebo. |Icncci 2O11,
DI:1O.1O161SO14O-6736(11)61383-4j
There have been concerns regarding
CLTI inhibilors folloving lhe failure of
lorcelraib lhe hrsl CLTI inhibilor de-
veloed in lhe ILLUMINATL*** lrial. Al-
lhough lhe drug raised HDL choleslerol by
72 ercenl and decreased LDL choleslerol by
25 ercenl, ILLUMINATL vas halled in De-
cember 2OO6 because of a signihcanl increase
in cardiovascular evenls and morlalily in lhe
lrealmenl grou.
In conlrasl lo lorcelraib, dalcelraib
did nol have an effecl on AIM |ambulalory
blood ressure moniloringj, roviding fur-
lher reassurance regarding lhe safely of lhe
comound, said Luscher. He added lhal lhe
dal-VLSSLL lrial demonslraled lhe feasibil-
ily of using IMD lo lesl lhe inuence of nev
cardiovascular comounds on lhe biology of
lhe vessel vall and endolhelial funclion.
Dr. Keilh Iox, Irofessor of Cardiology,
Universily of Ldinburgh in Ldinburgh, Scol-
land, UK and residenl of lhe rilish Car-
diovascular Sociely, hovever caulioned lhal
given lhe limiled size of lhis lrial il's only
vhen lhe large hase III lrial is comleled
lhal ve vill knov for sure vhelher lhese
aarenl modesl changes in I are real and
vhelher lhey have an adverse effecl on oul-
comes.
Ilans for a hase III lrial of dalcelraib
called lhe dal-UTCML
1
lrial include lhe
enrolmenl of 15,6OO alienls vilh resulls ex-
ecled in 2O13. LM
* !c|-V|SS|I. Vcscu|cr cjjccis cn! scjciq cj
!c|ccircpi| in pciicnis uiin cr ci risk cj ccrcncrq
nccri !isccsc
** !c| PIAQU|. Scjciq cn! cjcccq cj !c|ccircpi|
cn cincrcsc|crciic !isccsc using nctc| ncn intcsitc
mu|iimc!c|iiq imcging
*** |IIUM|NA1|. |ntcsiigciicn cj Iipi! Ictc|
Mcncgcmcni ic Un!crsicn! iis |mpcci in
Aincrcsc|crciic |tcnis
1
!c|-OU1COM|. |jcccq cn! scjciq cj !c|ccircpi|
in pciicnis uiin rcccni ccuic ccrcncrq sqn!rcmc
ROCKET-AF: Rivaroxaban matches warfarin
Nove| HDL-raising drug appears safe
<< |rcm pcgc 1
RIvarnxaban mct thc
crItcrIa Inr nnn-InIcrInrIty

ApIxaban sIgnIcant!y rcduccd thc rc!atIvc rIsk

nI strnkc nr systcmIc cmbn!Ism by 21 pcrccnt

Conf er ence Cover age

October 2011
09
Pharmacoeconomics of Diabetes: Evaluating the
Return on Investment for Medical Nutrition Therapy
Jeffrey Mechanick
Clinical Professor of Medicine,
Division of Endocrinology, Diabetes and Bone Disease,
The Mount Sinai Medical Center,
New York, NY
Glycaemic variability contributes to the development of diabetes-related
microvascular complications, a leading cause of blindness, renal failure and nerve
damage, along with macrovascular complications such as myocardial infarction,
stroke and limb amputation due to diabetes-accelerated atherosclerosis. In
particular, hyperglycaemic excursions lead to an overproduction of superoxide,
which is instrumental in initiating the disease process.
1
In the past, fasting blood
glucose measurements alone were considered to be the key to maintaining
glycaemic control. However, the role of postprandial glucose excursions in
inuencing overall glycaemic control and HbA1c levels is increasingly being
acknowledged. Data shows that postprandial glucose has a greater impact at
lower levels of HbA1c, while fasting blood glucose levels predominantly inuence
HbA1c as the diabetes worsens.
2

The comprehensive management of diabetes involves a holistic approach that
is not focussed on HbA1c management alone, but also entails management of
other factors such as blood pressure, weight and cholesterol level, and involves
a comprehensive approach including nutrition, exercise and medication, as well
as self-care.
Medical Nutrition Therapy (MNT) for Diabetes
Evidence strongly suggests that nutritional intervention may protect against
cardiovascular disease, especially in diabetic patients.
3,4
The main aim of medical
nutritional therapy (MNT) in diabetes is to achieve and maintain blood glucose
levels in the normal range or as close to normal as is safely possible, together
with a lipid and lipoprotein prole that reduces the risk of vascular disease, and
the blood pressure levels within or close to the normal range. In addition, MNT
is intended to prevent or at least slow down the rate of development of the
chronic complications of diabetes by modifying nutrient intake, while addressing
individual nutritional needs by taking personal and cultural preferences and
willingness to change into account. Clinical trials and outcome studies of MNT
have reported reductions in HbA1c of 1% in type 1 diabetes and 1-2% in type 2
diabetes, depending on the duration of diabetes.
5,6
Diabetes Specic Formulas, as a part of MNT, should have low carbohydrate
content, containing primarily slowly digesting carbohydrates that prevent brisk
glycaemic excursions. It should have high bre content and preferably include
fructose as the sweetener (if needed), as fructose has a minimal impact on blood
glucose and exhibits a relatively small insulin response. Furthermore, exible use
of the supplement either as a low calorie meal or meal supplement, a snack or as
a sole source of nutrition for tube feeding should be possible.
7

The LOOK AHEAD Research Group conducted a study to determine the
effectiveness of intentional weight loss in reducing cardiovascular disease
event rates in type 2 diabetes. Patients with type 2 diabetes and BMI greater
than 25 kg/m
2
were randomised to receive multi-component intensive lifestyle
intervention (ILI) involving portion-controlled diets that included liquid meal
replacements, ongoing regular contact throughout follow-up period, weight
loss medication(s), and advanced behavioural strategies to reduce weight, or
standard diabetes care. Meal replacements were an important part of LOOK
AHEAD weight loss intervention. The planned follow-up period was 11.5 years.
Analysis of one year results of LOOK AHEAD showed an average 8.6% reduction
in body weight with ILI, with a greater proportion of ILI participants reporting
reduced intake of diabetes, hypertension, and lipid-lowering medications. Of
note, mean HbA1c reduced signicantly in the ILI treated group [7.3 to 6.6%
(P<0.001)] as compared to the usual diabetes care group [7.3 to 7.2%]. Signicant
improvements were also observed in systolic and diastolic pressures, triglycerides,
HDL cholesterol and urine albumin-to-creatinine ratio with ILI versus standard
treatment of diabetes.
8
The LOOK AHEAD results have been incorporated into
the 2009 American Diabetes Association position statement which states that the
use of meal replacements once or twice daily instead of a usual meal can result in
signicant weight loss.
A prospective, randomized clinical trial evaluated the impact of a structured
intervention in overweight Chinese diabetic patients. The intervention group
of 100 patients received comprehensive management with diabetes education,
frequent blood glucose monitoring, nutritional counselling, meal plans with
diabetes-specic nutritional meal replacement and weekly progress updates with
the study staff. In contrast, the control group of 50 patients received diabetes
education including diet and physical activity instructions alone. At 12 weeks, the
integrated treatment approach was found to result in signicant improvements in
body weight, glycaemic control, and markers of cardiovascular health [Figure 1].
9
Tatti and co-workers further assessed whether addition of low glycaemic diabetes-
specic nutritional formulas to a structured intervention program could improve
the weight loss and metabolic control of obese subjects with type 2 diabetes
who were resistant to weight reduction. The researchers conrmed signicant
reduction in weight and HbA1c levels at 6 months follow-up with the structured
intervention program [Figure 2].
10
Clinical trial results were used to develop models that were representative of
outcomes related to type 2 diabetes. A series of comparisons were done in which
diabetes specic nutritional interventions were compared to traditional therapy
regimens under varying cost and effective conditions. It was seen that with certain
scenarios, diabetes-specic nutrition was found to be cost-saving, particularly
when it was used effectively as part of a structured intervention program.
In summary
Diabetes-specic nutrition is a cost-effective way to help manage diabetes, as it
results in clinical and economic benets by helping to prevent or delay diabetes
complications.
References
1. Brownlee M. Nature. 2001;414(6865):813-20. 2. Monnier L, et al. Diabetes Care 2003;26:881-885. 3. Franz MJ, et al. J
Am Diet Assoc. 2010 Dec;110(12):1852-89. 4. Riccardi G, et al. Am J Clin Nutr. 2008 Jan;87(1):269S-274S. 5. Pastor JG et al.
Diabetes Care 2002 Mar;25(3):608-13. 6. Pastor JG et al. J Am Diet Assoc. 2003 Jul;103(7):827-31. 7. Via MA, et al. Curr Diab
Rep. 2011 Apr;11(2):99-105. 8. Look AHEAD Research Group. Diabetes Care. 2007 Jun;30(6):1374-83. 9. Sun J, et al. Asia Pac
J Clin Nutr. 2008;17(3):514-24. 10. Tatti P, et al. Mediterranean Journal of Nutrition Metabolism. 2010;3:65.
Figure 1: Changes in body weight with MNT in overweight Chinese diabetic patients
76.5
76.0
75.5
75.0
74.5
74.0
73.5
73.0
72.5
72.0
71.5
kg
Baseline
75.6
75.7
Control Intervention
72.8
P<0.0001
74.3
Mid-term End
Figure 2: Changes in HbA
1c
with MNT in overweight Chinese diabetic patients
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
HbA1c (%)
Baseline
>5% Wt loss <5% Wt loss
+ Meal Replacement
(n=29)
7.0 1.5
6.7 1.5
>5% Wt loss
(n=40)
<5% Wt loss
(n=38)
(n=96)
3 months 6 months
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The Role of Medical Nutrition Therapy in the
Comprehensive Management of Type 2 Diabetes
T
he global prevalence of type 2 diabetes has reached epidemic proportions, with India and China being the major
contributors to this growth. Furthermore, there are a large number of undiagnosed pre-diabetic patients who are at
an increased risk of developing diabetes. Complications of diabetes have far-reaching effects on almost every organ of
the body, impacting the overall quality of life of the patient.
At a lunch symposium held in conjunction with the Asian Congress of Nutrition in Singapore on the 14th of July 2011,
Professor Jeffrey Mechanick, Clinical Professor of Medicine, Division of Endocrinology, Diabetes and Bone Disease at
the Mount Sinai School of Medicine, highlighted how the introduction of medical nutritional therapy within the model
of type 2 diabetes treatment resulted in substantial downstream benets by preventing diabetic complications and
contributed to meaningful gains in health-economic terms.
Sponsored Symposium Highlights
Si ngapor e Focus
October 2011
13
ossibly also immunomodulalory
funclions.
As lhese funclions cannol be
rovided by exisling arlihcial de-
vices, scienlisls have long been lry-
ing lo include in lhem bioreaclors
incororaling live human renal
cells, so lhal such devices could
erform human kidney's lubular
funclions as vell.
Hovever, lhe roximal lubule
cells from human kidneys have nol
survived on lhe olymeric mem-
branes currenlly used in hemodi-
alysis carlridges.
We have develoed a orous
membrane as vell as coalings for
convenlional membranes lo vhich
human roximal lubule cells suf-
hcienlly adhere lo form eilhelia.
This is crucial for lhe arlihcial bio-
reaclor lhal vill erform many of
lhe funclions of a nalural human
kidney, said Zink.
We are nov roceeding vilh
animal sludies on our |bioarlih-
cial kidneyj device and hoe lo
reach lhe clinical sludies slage in 5
years, she added.
IN is one of lhe leading re-
search bodies under lhe umbrella
of lhe Agency for Science Technol-
ogy and Research (A*STAR).
Rajesh Kumar
S
cienlisls al lhe Inslilule of
ioengineering and Nano-
lechnology (IN) in Sin-
gaore have overcome a ma|or
hurdle in lhe develomenl of so-
hislicaled bioarlihcial kidneys
vhich may hel imrove lhe sur-
vival rale and recovery of crilically
ill alienls suffering from acule
kidney failure.
Desile several advancemenls
in lhe held of arlihcial kidneys,
lhe high morlalily rale (5O lo 7O
er cenl) in such alienls has nol
changed over lhe decades.
y develoing a orous mem-
brane lhal is comalible vilh hu-
man kidney cells, lhe IN scienlisls
have crealed a bioreaclor lhal can
be used in arlihcial devices, rod-
ding lhem lo mimic many of lhe
comlex funclions lhal human kid-
neys erform.
This could imrove lhe lifesan
and qualily of life for end-slage re-
nal disease alienls vho are eilher
availing lranslanls or cannol gel
one due lo olher comorbidilies,
said Irofessor Daniele Zink, IN
leam leader and rincial research
scienlisl, vho led lhe research leam
along vilh IN execulive direclor
Irofessor }ackie Ying.
Acule kidney failure is becom-
ing a huge issue globally, due lo an
alarming increase in kidney failure
cases folloving a diabeles eidem-
ic.
Arlihcial kidneys are essenlial-
ly dialysis machines lhal erform
hemodialysis and remove uremic
loxins and vasle from lhe body.
ul a human kidney has a variely
of addilional comlex funclions
including reabsorlion of glucose,
amino acids and valer, and excre-
lion of xenobiolics, drugs and olh-
er organic comounds.
Kidneys also regulale lhe con-
cenlralions of sodium, olassium
and hoshorus, as vell as H bal-
ance. They conlrol blood volume
and ressure and have imorlanl
melabolic, endocrinologic and
5cientists a step c|oser to deve|oping
bioarticia| kidneys
Elvira Manzano
A
skincare roducl recenlly
launched in Singaore hels
lo alleviale a range of dermalo-
logical roblems, according lo ils
manufaclurer.
riginally develoed in Soulh
Africa, lhe skincare roducl (io-
il) has been shovn lo imrove
lhe aearance of scars, slrelch
marks and uneven skin lone in lhe
face and body in clinical lrials and
skin lesls.
In a recenl double-blind sludy
erformed in Germany, 36 sub-
|ecls aged 18 lo 65 vere random-
ized lo receive eilher aclive lreal-
menl vilh lhe skincare roducl or
lacebo lvice daily for 8 veeks.
|roDLRM sludy, dala on hlej
Afler 2 veeks, more lhan 65
ercenl of lhose receiving aclive
lrealmenl had a signihcanl re-
duclion in scars (as measured by
various alienl and observer as-
sessmenl scales). y lhe end of
lhe sludy, over 9O ercenl in lhe
lrealmenl grou shoved imrove-
menl in lheir scars comared vilh
lacebo. Iurlher dala reorled in-
dicaled lhal imrovemenl in scars
vas osilive correlaled vilh dura-
lion of lrealmenl.
Anolher 8-veek sludy also
conducled in Germany shoved
similar efhcacy resulls in favor
of lhe same roducl in reducing
slrelch marks or slriae.
The nev roducl conlains a
binding comonenl vhich aids
absorlion of ils ingredienls
vhich include vilamins A and L,
and nalural lanl oils such as lav-
ender, calendula, rosemary and
chamomile. As vell as imroving
scars, slrelch marks and uneven
skin lone, lhe manufaclurer also
claims lhal il is effeclive al im-
roving dehydraled skin and olh-
er skin condilions associaled vilh
aging.
Promising new skincare product
enters 5ingapore market
1nc ncu prc!uci ncs |ccn sncun in c|inicc| iric|s ic imprctc inc cppccrcncc
cj sccrs cn! sircicn mcrks.
|BN |cc! rcsccrcncr Prcjcsscr Dcnic|c Zinc (piciurc!) cn! iccm nctc
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MTOCT15-11/001
Reference: 1. Approved PI.
1
Si ngapor e Focus
October 2011
15
Elvira Manzano
A
leam of doclors from Sin-
gaore has clinched a glob-
al avard for lheir efforls lo
romole ublic avareness againsl
slrokes caused by alrial hbrillalion.
Dr. Deidre Anne De Silva, a
consullanl al lhe dearlmenl of
neurology, Nalional Neurosci-
ence Inslilule (Singaore General
Hosilal Camus) and her leam
received -1O,OOO (aboul S$17,43O)
for lheir vinning ro|ecl Avare-
ness and Ieedback for Alrial Iibril-
lalion alienls (AI for AI).
Their enlry vas among 32 vin-
ners chosen by lhe ublic and a
anel of exerls in lhe global cam-
aign 1 Mission, 1 Million Gelling
lo lhe Hearl of Slroke. The ro|ecl
is suorled by over 45 lhird-arly
organizalions around lhe vorld
and is sonsored by oehringer
Ingelheim, vhich donaled -1 mil-
lion for lhe global camaign lo re-
venl one million alrial hbrillalion
slrokes lhrough ublic avareness
camaigns.
The avard ceremony vas held
in Iaris.
The ro|ecl rize money vill
fund lhe educalion camaign lhal
our doclors here vill launch, lar-
geling alienls vilh alrial hbril-
lalion. This rogram aims lo raise
avareness of available lrealmenls
lo reduce slroke risk vilh alrial
hbrillalion and lo recognize lhe
symloms of slroke should il un-
forlunalely occur so lhey may re-
ceive medical care as soon as os-
sible, she said.
We are roud of Singaore
being among lhe global vinners.
The ublic educalion inilialive lhal
lhe Singaore doclors vill lead
is limely and hoefully, vill save
many lives, said Shavn Chong,
markeling manager of oehringer
Ingelheim.
lher vinners included lhe
designers of an IIhone a lo de-
lecl an irregular rhylhm and lhe
roduclers of a disease avareness
video.
As for lhe Singaore leam's
ro|ecl, lhe camaign vill slarl
vilh lhe dislribulion of educa-
lional lools such as cuslomized
brochures, videos and oslers on
slroke symloms and manage-
menl lo 1,OOO AI alienls here.
Lmovering alienls vilh alrial
hbrillalion vilh knovledge of lheir
condilion and ils managemenl is
imorlanl, De Silva said.
Ialienls vilh AI are hve limes
more likely lo suffer a slroke, bul
many of lhem are nol avare of
lheir risk and lake no aclion lo re-
venl il.
Greg Town
T
his year's Asian Iacihc Diges-
live Week (AIDW) in Singa-
ore sav a large lurnoul of del-
egales and leaders in funclional and
inammalory gaslroinleslinal dis-
orders, advanced endoscoy and
liver diseases.
Held al Sunlec Inlernalional
Convenlion and Lxhibilion Cen-
lre, lhe conference consisled of
lhree inlensive days of lenary
and slale of lhe arl leclures and
symosia as vell as a hosl of re-
conference osl-graduale courses,
a live vorksho and, a arlicu-
lar highlighl, a hands-on animal
model endoscoy vorksho.
Conference residenl Irofes-
sor Lng-Kiong Teo said lhere vere
some exciling inclusions in lhe ro-
gram for lhis year, vhile alvays
keeing in mind an Asian Iacihc
focus.
The AIDW has grovn in sig-
nihcance over lhe years, said Teo.
In lhe asl, Asian gaslroenlerolo-
gisls vill look lo lhe Wesl for rac-
lice guidelines and clinical dala in
order lo beller care for lheir a-
lienls. Hovever, ve nov realize
lhal lhe disease rocess and ils
managemenl differ for individu-
als of differenl race and cullural
backgrounds vhich is vhy lhe
AIDW vas eslablished in lhe hrsl
lace.
5ingapore neuro|ogists win g|oba| stroke award
APDW comes
to 5ingapore
Prcjcsscr Picrcc Cncu cj Singcpcrc
!c|itcrs c prcscniciicn !uring APDW
2011
AEDs = Antiepileptic drugs
AIgorithm for Medication SeIection in Chronic
Pain with and without Comorbid Depression
Nociceptive Pain
Evaluate risks
Secondary Sleep
Disturbance
Secondary
Depression
Persists after
adequate analgesia
Evaluate risks
Evaluate risks
SSR
Trial
SNRs
Primary
Depression
Short-term NSADs,
COX-, Opioid
Evaluate risks
Persists after
adequate analgesia
Antihistamine.
Zolpidem, Low-dose
benzodiazepine
Trazodone
Low dose TCA
Lidocaine patch
AED (Ca
+
& Na
+

channel) Alpha 2
agonists
Titrate TCA
(Na
+
channel and
SNR)
Neuropathic Pain
Pain condition
comorbid depression
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. ;...-a.a.ac-c.-.s.--.-;-ss.._ac_;a.
.. .-.s. c - a. s... -s,.a, ..-
Better Outcomes for Patients
with Pain and Depression
Pain and depression share an intimate relation and a large proportion of patients in pain suffer from
clinical depression. At the recent 4
th
ASEAPS conference in Thailand, Dr Lee Wing-King, Clinical Associate
Professor (Honorary), Departments of Psychiatry and Community and Family Medicine, Chinese University
of Hong Kong, elaborated on the relationship between pain and depression and discussed the currently
available treatment options for such situations.
This publication is made available to the medical profession through an unrestricted educational grant fromPfzer.
Editorial development by UBMMedica Medical Education.
The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor; any liability
or obligation for loss or damage howsoever arising is hereby disclaimed.
2011 TIMS (Thailand) Ltd. All rights reserved. No part of this publication may be reproduced by any process in any
language or format without the written permission of the publisher.
TIMS (Thailand) Ltd. 58-60 Sukhumvit 62, Bangjak, Prakanong, Bangkok 10260
Tel: +66-2-7415354 Fax: +66-2-7415360
E-mail: enquiry.th@ubmmedica.com Web site: www.ubmmedica.com
Sponsored symposium highlights
t._.~ . tttt ~c .;c:~c: :~c:c .c o~;~...cc
t._.~ ~~.~:.cc.|.; r~:.~~c c|cc.c ;~.c ~co Vtt
Si ngapor e Focus
October 2011
17
Elvira Manzano
A
nev melhod of corneal re-
lacemenl is nov available
in Singaore, offering fresh
hoes lo olhervise deserale a-
lienls vho had failed corneal grafls
or vilh blinding corneal diseases.
Lighl alienls vilh various cor-
neal diseases undervenl oslon
Keraloroslhesis (arlihcial cornea)
surgery under Dr. Leonard Ang,
medical direclor and senior con-
sullanl ohlhalmologisl al lhe Lye
and Cornea Translanl Cenlre, Sin-
gaore. Ang lrained in lhe US vilh
vorld-renovned cornea secialisl
Dr. Claes Dohlman, vho ioneered
lhe oslon Keraloroslhesis roce-
dure.
A female alienl from Malay-
sia, vho requesled anonymily, said
Ang oeraled on her lefl eye in
May 2O11. She had been blind for
3 years bul vilhin 2 monlhs afler
lhe surgery, she regained almosl
erfecl vision (617.5).
Anolher alienl, a viclim of an
acid allack in China 7 years ago,
soughl Ang's hel afler lhree failed
cornea lranslanls. Deserale lo
regain her vision, she undervenl
oslon Keraloroslhesis surgery
in Augusl 2O11 and vas able lo see
vell 3 veeks afler.
The same slory goes for six olh-
er alienls of Ang vho achieved
9O lo 95 ercenl of lheir visual o-
lenlial afler surgery. All, excel for
one alienl vho had re-exisling
nerve damage, achieved a 6112
vision (driving vision), or beller,
afler undergoing arlihcial cornea
lranslanls.
This enabled lhem lo reslore
long-lerm vision and resume lheir
normal daily aclivilies, said Ang.
He said many foreign alienls
from Taivan, China, Canada, Iaki-
slan, Lasl Timor and lhe US have
since ovn in for lhis arlihcial cor-
nea surgery.
The rocedure is done by in-
serling a collar bullon-shaed de-
vice inlo a corneal grafl and lhen
suluring il inlo lhe alienl's cornea
as in slandard lranslanlalion. The
nalural lens is lhen removed. Iinal-
ly, a sofl conlacl lens is alied lo
lhe surface. Surgery lakes a mini-
mum of 2 hours.
Ang said visual imrovemenl
is usually seen vilhin days or
veeks afler lhe surgery. Visual re-
covery is much fasler and vision is
much beller lhan convenlional cor-
neal lranslanls.
He added lhal arlihcial cor-
nea relacemenl is lhe lrealmenl
5eries of articia| cornea transp|ants
performed in 5ingapore
of choice for alienls vilh severe
corneal oacily or mullile failed
corneal grafls, or lhose vilh severe
deslruclive eye surface diseases
and loss of slem cells from chemi-
cal in|ury or severe inammalion
and scarring.
The hrsl oslon Keraloros-
lhesis surgery received IDA clear-
ance in 1992. To dale, more lhan
4,5OO imlanlalions have been er-
formed vorldvide, mainly in lhe
US and Luroe. Aboul 1OO vere
done in Asia.
Around 2O million eole suf-
fer from corneal blindness vorld-
vide, making il lhe second mosl
common cause of lrealable blind-
ness afler calaracls. Convenlional
cornea lranslanls also involve re-
lacing lhe diseased cornea vilh a
heallhy cornea lranslanl. Hovev-
er, vhile lhese rocedures can suc-
cessfully reslore sighl lo alienls,
lhey have an underlying risk of
cornea grafl re|eclion and failure.
Arlihcial cornea lranslanls offer
hoe for alienls vho have re|ecl-
ed mullile convenlional cornea
lranslanls in arlicular.
1nc Bcsicn Kcrcicprcsincsis is
ircnsp|cnic! cnic inc pciicnis cqc
cn! sccurc! in p|ccc uiin siiicncs.
|Fnr thc rccIpIcnts],
thIs cnab!cd thcm
tn rcstnrc !nng-tcrm
vIsInn and rcsumc thcIr
nnrma! daI!y actIvItIcs

Cblloren wltb atoplc oermatltls are ln constant cycle o| ltcb ano scratcb tbat can leao to skln oamage ano reouceo
quallty o| ll|e. Atoplclalr" ls a non steroloal symptomatlc treatment |or mllo to mooerate atoplc oermatltls tbat ls
unlquely proven ln robust cllnlcal trlals to slgnl|lcantly reouce ltcb ano tame |lares
1,2
, tbereby belplng to break tbe
vlclous ltcb-scratcb-worry cycle.
Atoplclalr" ls speclally |ormulateo wltb key lngreolents tbat bas antl-ln|lammatory propertles to qulckly calm ltcb ano
burnlng sensatlons, bas antl-oloant e||ect ano provloes key pbyslologlc llplo ano byoratlon to repalr ano protect skln
barrler.
Flnally, Atoplclalr" can belp set your patlents |ree |rom tbe vlclous cycle o| atoplc oermatltls.
Invida (Singapore) Private Limited 79 Science Park Drive #05-01, Cintech IV, Singapore Science Park One, Singapore 118264
IN
V
/
A
T
P
/
S
G
/
0
0
4
/
1
0
1
1
4.9
18.6
21.0
25.1
37.7
61.4
65.3
66.6
0 10 20 30 40 50 60 70
Genitalia
Feet
Nails
Hands
Others
Scalp
Lower limb
Upper limb
I
n
v
o
l
v
e
d

r
e
g
i
o
n
s

n=886
The SELECT Study: An Asian, Prospective, Open-Label
Study in Patients with Plaque Psoriasis
of Disease Questionnaire (PADQ). This completed,
initial PADQ was considered the baseline. Every set
of questionnaire for each patient was pre-assigned
with unique site and patient numbers and only the
patient initials had to be lled-in by the dermatologist.
The questionnaires included questions on previous
anti-psoriatic medication(s), body parts affected by
psoriasis and physician assessment of disease, mainly
by a combination of clinical examination and body
surface area; some physicians utilised Physician Global
Assessment (PGA), Psoriasis Area and Severity Index
(PASI), and Quality of Life (QoL). All patients enrolled
in the study were put on the two-compound ointment
therapy for 4 to 8 weeks. The second PADQ was
completed for patients who returned for follow-up after
approximately 4 weeks. The patient was then required
to answer the Patient Satisfaction Survey (PSS) for week
4, including 6 questions such as the level of satisfaction
with the study medication, reason for satisfaction or
dissatisfaction and effect of treatment on quality of life
(QoL) based on whether they were bothered by the
itchiness, embarrassed or self-conscious due to the
disease, and the impact on social or leisure activities.
Continuing treatment with the two-compound ointment
for another 4 weeks was entirely up to the discretion of
the dermatologist. The third PADQ was completed for
patients who returned for follow up after approximately
8 weeks. The patient was then required to answer the
Patient Satisfaction Survey (PSS) for week 8.
This study was not designed to test a formal hypothesis
or mandate the use of study medication. Patient
therapy was at the discretion of the treating physician.
To minimize the possibility of centre-imposed bias,
participating dermatologists agreed to seek the consent
for participation of all patients meeting the eligibility
criteria seen at the site and sequentially enrolling them.
Results
A total of 886 patients were enrolled into the SELECT
study and more than 85% of the patients completed
PADQ and PSS at week 4, while approximately 20%
completed PADQ and PSS at week 8 during the optional
second follow up. All the patients were included for the
safety analysis. The gender distribution of the study
group was relatively equal - with 51% males and 49%
females.
The SELECT study included 886 patients
from various sites in Asia, with equal
gender distribution
Inclusion/Exclusion Criteria
Inclusion
Patients with stable plaque psoriasis vulgaris, aged 18 years
or above, with informed consent
Exclusion
Current diagnosis of guttate, erythrodermic, exfoliative or
pustular psoriasis
Treatment with systemic anti-psoriatic treatment, PUVA
therapy, UVA therapy or topical anti-psoriatic treatment for
psoriasis of the trunk or limbs, within the 2-week period prior
to baseline visit
Methods
Subjects who received anti-psoriatic treatments
as dened by the exclusion criteria were required
to complete a washout period of at least 2 weeks
prior to initial visit (Table 2). On subjects initial visit
(Week 0), the dermatologist prescribed calcipotriol/
betamethasone dipropionate combination ointment
as per his/her discretion. The dermatologist asked the
patient for his/her interest in participating in the study
only after the prescription was made, and patients were
given the choice to refuse or accept the enrolment.
Once the patient was enrolled into the study, the
dermatologist answered the Physician Assessment
MY PH SG LK TH VN To-
tal
Number of
enrolled patients
47 493 12 19 141 174 886
Treated patients 47 493 12 19 141 174 886
Withdrawals/drop outs 0 0 0 0 0 0 0
Study
Completion
PADQ
Week 4
45 408 12 19 141 166 791
PADQ
Week 8
14 105 6 0 0 58 183
PSS Week 4 42 389 12 19 141 166 769
PSS Week 8 14 91 6 0 0 58 169
Safety population 47 493 12 19 141 174 886
MY-Malaysia; PH-Philippines; SG-Singapore; LK-Sri Lanka; TH-Thailand;
VN-Vietnam
Table 1: Patient demographics
Figure 2: Regions affected by psoriasis
Table 2: Inclusion/exclusion criteria
Approximately one-third of the study population was
suffering from psoriasis for more than 6 years and close
to two-thirds of the patients had plaque psoriasis on
their upper & lower limbs, followed by scalp psoriasis
(60%). This was consistent with epidemiology data from
Western countries which states that scalp psoriasis has
an incidence of 50% to 80% (Figure 2).
1
Regions Involved
Figure 1: The SELECT study ow
OPTIONAL
~2 weeks washout where necessary
Baseline Visit (Week 0)
Follow-up Visit 1 (Week 4)
Follow-up Visit 2 (Week 8)
Collection of
completed forms
Data analysed by Clinical
Research Organisation
Study Flow
Study enrolment
Epidemiology of psoriasis in Asia is
similar to that in Western countries
As expected, the study data indicated that topical
therapy is the most widely accepted option in the Asia-
Pacic, with more than three-quarters of the patients
being on some sort of topical therapy in the past 6
months.
Topical therapy remains the most
widely accepted treatment modality in
the Asia-Pacic region
Background
Even though plenty of data is available on the
treatment of psoriasis through numerous clinical trials
conducted in Europe and North America, data on Asian
populations seem to be limited to date. The SELECT
study was conducted with the overall objective of lling
this gap by collecting Asian data on the effectiveness of
calcipotriol/betamethasone dipropionate combination
ointment (Daivobet

) in psoriasis and its impact on

the Asian patients quality of life. It was a multicentre,
prospective, observational, phase IV study in patients
with stable plaque psoriasis vulgaris from different
Asian countries including Malaysia, Philippines,
Singapore, Sri Lanka, Thailand and Vietnam (Table 1).
The study aimed to analyse clinical experiences in using
the two-compound ointment in psoriasis, assessing the
effectiveness over a 4 to 8-week period and recording
and evaluating patient experiences.
The SELECT study was designed to
address the limited Asian data on
psoriasis, with particular focus on
the role of calcipotriol/betamethasone
dipropionate combination
ointment treatment
Abstract
Background and Objectives: Currently, there is limited data on the management of psoriasis in Asia. The SELECT study was an Asian, multicentre, prospective, observational, phase
IV study in patients with stable plaque psoriasis, designed to record and evaluate efcacy as well as clinical and patient experiences with the use of calcipotriol/betamethasone
dipropionate combination ointment (Daivobet

).
Methods: This was an observational study, which included 886 patients aged *18 years with stable plaque psoriasis vulgaris after informed consent. The study involved 50
investigation sites in Thailand, Philippines, Malaysia, Singapore, Sri Lanka and Vietnam. In those who were already on treatment, a 2-week washout period without any treatment
was advised. The exclusion criteria included current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.
Results: Majority (30.5%) had psoriasis for more than 6 years. All the patients were given the two-compound ointment treatment, which offered rapid symptom relief by 2 weeks.
By 4 weeks (n=791), 79.1% of the patients were declared by treating physicians as having mild or absent disease, as compared to 36.9% at baseline. Notably, 18.2% achieved
complete resolution of the symptoms at 4 weeks and only 20.8% had moderate or more disease at 4 weeks (as compared to 63.1% at baseline, a reduction by one-third). A
total of 96.5% were either satised or very satised with the treatment, mainly due to efcacy and ease of use, followed by rapid onset of action and better tolerability
with minimal side effects. More than 90% of the patients reported signicant improvements in Quality of Life (QoL) at the end of 4 weeks, with symptoms having negligible
impact on QoL by then. This probably translated into a high compliance rate of 95.2% with the two-compound ointment treatment at 4 weeks. After 8 weeks of treatment with
the two-compound ointment (n=183), 28.4% of the patients had absent, and 0% had very severe disease, which probably led to 97.6% of the patients being either satised
or very satised with the two-compound ointment (48.5% very satised at 8 weeks vs. 34.2% at 4 weeks, n=169).
Conclusion: Calcipotriol/betamethasone dipropionate combination ointment is an effective treatment for psoriasis across all disease severities, and offers high level patient
satisfaction due to efcacy, ease of use, rapid onset of action (within 2 weeks) and tolerability. Further investigation into the use of this two-compound ointment in sequence or
in combination with other treatment modalities will provide further insights into effective management of psoriasis.
SELECT: Satisfaction & Efcacy LEvels With Calcipotriol & BeTamethasone
Percentage of patients (%)

5.3
46.9 47.7
10
48.6
41.4
7.8
44.7
47.5
0
10
20
30
40
50
60
A lot A little Not at
all
A lot A little Not at
all
A lot A little Not at
all
Skin irritation* Embarrassment** Interference with
social life***
P
e
r
c
e
n
t
a
g
e

o
f

p
a
t
i
e
n
t
s

(
%
)

*Over the last week how itchy sore painful or stinging has the patients skin been?
**Over the last week how embarrassed or self conscious has the patient been on the skin?
***Over the last week how much has the patients skin affected any social or leisure activities?
n=769

36.9
52.1
9.4
1.6
60.9
18.5
1.8
0.5
28.4
55.7
12
1.6
0
0
10
20
30
40
50
60
70
Absent Mild Moderate Severe Very Severe
P
e
r
c
e
n
t
a
g
e

o
f

p
a
t
i
e
n
t
s

(
%
)

Baseline
4 weeks
8 weeks
n=183

18.2
0.1
3.4
62.3
34.2
0 10 20 30 40 50 60 70
Very
disappointed
Disappointed
Satisfied
Very
satisfied

n=769
Reason behind high satisfaction % Patients
Efficacy 80.5%
Ease of use 67.9%
Rapid onset of action 52.0%
Minimal side effects 43.0%
0
36.9
52.1
9.4
1.6
18.2
60.9
18.5
1.8
0.5
0
10
20
30
40
50
60
70
Absent Mild Moderate Severe Very Severe
P
e
r
c
e
n
t
a
g
e

o
f

p
a
t
i
e
n
t
s

(
%
)

Baseline
4 weeks
n=791
0
0.5
1
1.5
2
2.5
3
N
u
m
b
e
r

o
f

w
e
e
k
s

MY
Redness Plaque thickness Scaliness
PH SG LK TH VN Overall
n=769

0
36.9
52.1
9.4
1.6
0
10
20
30
40
50
60
Absent Mild Moderate Severe Very Severe
P
e
r
c
e
n
t
a
g
e

o
f

p
a
t
i
e
n
t
s

(
%
)

n=886
Baseline data
The majority of the patients had severity of moderate
or more, accounting for approximately two-thirds of the
patients enrolled into the study. Approximately one-
third had mild disease (Figure 3).
A total of 221 patients were shown to t these criteria
and patient assessments at 4 weeks and 8 weeks
were analysed to see if the two-compound ointment
treatment is effective in this group of patients. Among
these, approximately 20% of the patients were shown
to achieve absence of disease at 4 weeks. Similarly,
the proportion of patients with severe-to-very severe
disease (approximately 10% at baseline) also reduced to
<2% at 4 weeks. These data indicate that patients who
had been on steroid monotherapy experienced additional
benets from the two-compound ointment therapy.
After 4 weeks of treatment with the two-compound
ointment, approximately 97.5% of the patients were
either satised or very satised with the treatment.
Majority of the patients on calcipotriol/betamethasone
dipropionate combination ointment considered efcacy
and ease of use as the key contributing factors towards
treatment satisfaction, followed by rapid onset and
better tolerability.
Switching from steroid monotherapy to
the two-compound ointment therapy may
be a viable option in psoriasis
Among those who were on steroid monotherapy
for the last 6 months and were offered the two-
compound ointment for the rst time, a total of 55
patients completed 8 weeks of treatment. Data from
this subgroup of patients were specically looked at
and their disease severity tracked from baseline, to see
if the two-compound ointment treatment improves
the disease severity over time. Analysis of the
progression of their disease severity indicate that
treatment with the two-compound ointment improved
the proportion of patients with absent disease
considerably to 20% at 4 weeks, which more than
doubled to 44% at 8 weeks.
Similarly, the proportion of patients with mild
disease was improved from 16% at baseline to 50%
at 4 weeks and 49% at 8 weeks (slight reduction
from 4 weeks, probably due to higher proportion of
absent disease). Proportion of patients with moderate
disease was also reduced from 62% at baseline to
25% at 4 weeks, with a further reduction to 5% at
8 weeks. This data demonstrates that persistence
with the two-compound ointment treatment improves
disease severity considerably over time.
Calcipotriol/betamethasone dipropionate
combination ointment treatment offers
continual reduction in disease severity
with persistent therapy
Reference
1. Radtke MA, et al. Hautarzt. 2010;61(9):770-775.
Key Takeaways
The two-compound ointment was effective in
psoriasis across all disease severities
The two-compound ointment reduced the rate
of moderate-to-severe disease from >60% at
baseline to ~20% after 4 weeks of therapy
The two-compound ointment offered rapid
improvement in symptoms (within 2 weeks),
ensuring high level patient satisfaction
In patients who had been offered steroid
monotherapy prior to enrolment, switching
to the two-compound ointment helped in
reducing the disease severity
Approximately two-thirds of the
patients in the SELECT study had a
disease severity equal to or more
than moderate at baseline
Efcacy data at 4 weeks
Majority of the patients reported visible improvements in
the psoriatic lesion thickness, scaliness and redness at
4 weeks. The onset of action was rapid, with noticeable
changes within 2 weeks of initiating the two-compound
ointment treatment (Figure 4).
Figure 4: Onset of symptom relief
Figure 5: Disease severity at 4 weeks
Figure 6: Patient satisfaction and QoL at
4 weeks
Figure 3: Disease severity at baseline
Figure 7: Disease severity at 8 weeks
Sponsored as a service to the medical profession by
LEO Pharma.
Editorial development by UBM Medica. The opinions
expressed in this publication are not necessarily those of
the editor, publisher or sponsor. Any liability or obligation
for loss or damage howsoever arising is hereby disclaimed.
2011 UBM Medica. All rights reserved. No part of this
publication may be reproduced by any process in any
language without the written permission of the publisher.
UBM Medica Asia Pte Ltd, No. 3 Lim Teck Kim Road, #10-01
Genting Centre, Singapore 088934
Tel +65-6223 3788 Fax +65-6221 4788
Email enquiry.sg@ubmmedica.com www.ubmmedica.com
Calcipotriol/betamethasone dipropionate
combination ointment therapy offered
rapid symptomatic relief in patients with
psoriasis (within 2 weeks)
After 4 weeks of the two-compound ointment therapy,
an average 80% of patients had mild to absent
disease (as compared to 37% at baseline) and only
approximately 20% of the patients had equal to or
more than moderate disease severity at 4 weeks (as
compared to >60% at baseline), a reduction by one-
third. Notably, approximately 19.6% of the patients
achieved complete resolution of the symptoms at 4
weeks (Figure 5).
Analysis of the data on compliance with the treatment
demonstrated that >95% of the patients were compliant
with the psoriasis therapy with the two-compound
ointment. There was also high treatment satisfaction
and good QoL (Figure 6).
Efcacy data at 8 weeks
After 8 weeks of treatment, approximately 30% of the
patients were assessed as having absent (~20% at
4 weeks), and 0% were shown to have very severe
disease. By 8 weeks, less than 15% the patients had
a severity which was equal to or more than moderate
(~20% at 4 weeks) (Figure 7). Analysis of patient
satisfaction with treatment demonstrated that after 8
weeks of treatment with the two-compound ointment,
approximately 98% of patients were either satised
or very satised with the treatment. The proportion
of patients who were very satised with the treatment
was also shown to increase from ~34% at 4 weeks to
48.5% at 8 weeks.
Approximately 98% of patients were
either satised or very satised
with calcipotriol/betamethasone
dipropionate combination ointment
treatment at 8 weeks
Specic patient subgroups
A subgroup analysis was conducted subsequently on
patients who have been on steroid monotherapy for the
last 6 months, and being treated for the rst time with
the two-compound ointment. The aim of this analysis
was to understand how calcipotriol/betamethasone
dipropionate combination ointment-nave patients
respond to switching from steroid monotherapy to the
two-compound ointment.
Patient Satisfaction
Impact of Disease on QoL
Calcipotriol/betamethasone
dipropionate combination ointment
therapy for 4 weeks reduced the
proportion of patients with equal to or
more than moderate severity disease
by one-third, as compared to the baseline ubm
Disease severity at baseline
Percentage of patients (%)
Disease severity
Disease severity
Si ngapor e Focus
October 2011
20
Meningococca| vaccine |aunched in 5ingapore
5hocking myths on contraception persist
Rajesh Kumar
S
anoh Iasleur, lhe vaccines division of
Sanoh Grou, has launched Menac-
lra

, lhe hrsl quadrivalenl con|ugale

vaccine licensed for lhe revenlion of me-
ningococcal disease in Singaore.
Invasive meningococcal disease is one
of lhe leading causes of baclerial meningilis
(svelling of lhe brain or sinal cord) or me-
ningococcemia (blood infeclion) in Luroe,
US, Africa and Nev Zealand.
Allhough lhe disease is relalively un-
knovn in Asia and only a handful of cases
are reorled in Singaore each year, increas-
ingly mobile oulalions mean lhe lhreal of
lravellers bringing in lhe infeclion is becom-
ing slronger, said Dr. Adrian ng, hysician
senior consullanl vilh lhe dearlmenl of in-
feclious diseases al Tan Tock Seng Hosilal.
The infeclion can sread lhrough com-
mon everyday aclivilies, such as sharing
ealing ulensils and drinking glasses, kissing
and living in close quarlers like dormilories,
summer cams, large religious galherings
and army barracks.
The nev meningococcal vaccine offers
roleclion againsl four of lhe hve mosl com-
mon serogrous of lhe baclerium lhal cause
meningococcal infeclion, Neisseria menin-
gilidis serogrous A, C, Y and W-135 and
il is indicaled for eole aged from 2 lo 55
years, said Dr. Ihili sler, medical direc-
lor in global medical affairs al Sanoh Iasleur,
Lyon, Irance.
Invasive meningococcal disease can be
difhcull lo recognize, esecially in ils early
slages, because lhe inilial symloms are sim-
ilar lo lhose of more common viral illnesses.
Hovever, il can rogress quickly and may
cause dealh or disabilily in |usl a single day,
said ng.
aclerial meningilis can cause saslic
quadrilegia, hearing loss, cerebral edema,
cranial nerve alsies and menlal relardalion,
vhereas meningococcemia can lead lo loss
of limbs from gangrene, skin scars from ne-
crosis, renal failure, selic arlhrilis and eri-
cardilis.
Some eole can carry lhe bacleria in
lheir lhroal and remain asymlomalic, bul
ass il on lo lhe vulnerable grous such as
young children and lhe elderly, vho can
quickly develo lhe deadly disease, said
ng.
The Islamic Ha|| ilgrimage lo Mecca,
Kingdom of Saudi Arabia, has hislorically
been associaled vilh oulbreaks of meningi-
lis. Ior lhis reason, lravellers lo Mecca and
counlries in sub-Saharan Africa are currenlly
recommended vaccinalion vilh a olysac-
charide meningococcal vaccine.
Con|ugale vaccine rovides beller im-
mune resonse and hels reduce lhe circu-
laling baclerial load by revenling olenlial
carriers from acquiring lhe organism in lhe
hrsl lace, so lhey can no longer lransmil il
lo olhers, said sler.
Due lo lhe lack of such herd immunily
and ersislence of meningococcal carriers
among Ha|| ilgrims vaccinaled vilh lhe
olysaccharide vaccine, lhe Saudi Minislry
of Heallh has relaced local recommenda-
lions for meningococcal vaccinalion from
olysaccharide lo con|ugaled meningococcal
vaccine.
Singaore GIs could lherefore offer lhe
nev vaccine lo Ha|| ilgrims lo hel lhem
avoid becoming baclerium reservoirs lhal
could ul lheir loved ones al risk, said sler.
Il should be offered irreseclive of
vhelher lhe GI lhinks lhe alienl can afford
lhe vaccine or nol, he added.
Molhers of many children vho vere se-
verely affecled by meningococcal meningilis
lold me lhey vould have given a meningo-
coccal vaccine had lhey knovn before.
V
aginal douching vilh coca cola af-
ler sex, having sex in lhe balh, slay-
ing uside dovn for 2 hours afler sex and
vilhdraving lhe enis |usl before e|acula-
lion are some of lhe common mylhs aboul
conlracelion believed by young adulls in
Singaore, according lo a recenl survey.
These hndings are vorrying given lhal a
variely of conlracelive melhods are easily
available in Singaore and lhe level of ub-
lic avareness on heallh and sex educalion
is erceived lo be much higher here lhan
olher counlries in lhe region, said Irofessor
I.C. Wong, senior consullanl in obslelrics
and gynaecology al lhe Nalional Universily
Hosilal.
Tvo-hundred Singaorean men and
vomen aged 2O lo 35 years vere olled in
}uly, along vilh 1,6OO olhers from China,
India, Thailand, Soulh Korea, Iakislan, Tai-
van, Malaysia and Indonesia, as arl of an
Asia Iacihc survey lo undersland ublic ac-
cess lo accurale and unbiased informalion
on conlracelion.
A quarler of local resondenls believed
in al leasl one of lhe mylhs, vilh lhe main
sources of misinformalion being lhe inler-
nel, eers and religious leaders.
f arlicular nole, 81 er cenl of Singa-
ore resondenls said lhey had had unro-
lecled sex vilh a nev arlner and 6 ercenl
vere nol avare of any melhod of conlrace-
lion al all, bolh hgures being amongsl lhe
highesl in lhe region.
Dala suggesls young adulls in Singa-
ore do nol undersland lhe risk of regnan-
cy associaled vilh unrolecled sex, said
Wong. There is a ressing need lo carry on
roviding accurale and unbiased informa-
lion on conlracelion lo emover lhem lo
lake charge of lheir sexual and reroduclive
heallh.
The online survey seems lo have lhrovn
u a fev queslions of ils ovn. Ior inslance,
did lhe surveyors consider vhelher lhose
engaging in unrolecled sex vere married
and vere lrying lo conceive, or, vhelher
lhose vho had acknovledged having con-
lracelive mylhs vere nov any viser`
Whal vere lhe sexual heallh imlica-
lions of eole having sex vilhoul con-
doms vilh a nev arlner and hov can
heallh exerls engage vilh school and uni-
versily educalors, young adulls lhemselves
and religious leaders lo ensure lhey all gel
accurale informalion`
While acknovledging lhose queslions,
Wong said lhe scoe of lhe survey vas lim-
iled lo young adulls' level of avareness on
accurale conlracelive melhods and lhe
hndings did highlighl lhe facl lhal lhey
need lo lalk lo lheir doclors aboul il.
While GIs are vell laced lo broach lhe
sub|ecl and ask lheir alienls aboul lheir
sex life and conlracelive melhods, Wong
said lheir lale is robably already full
vilh more ressing heallh issues including
chronic diseases and seasonal ailmenls.
Al a olyclinic, a GI has lo see maybe
one alienl every 5 or 1O minules. In lhal
lime, il can be difhcull lo iniliale discussion
on reroduclive heallh and give delailed
advice on vhal's besl for lheir arlicular
silualion, said Wong, adding lhe challenge
nov is lo come u vilh a solulion lhal vill
be accelable lo all.
Ccnircccpiicn. gciiing inc jccis rigni, vas
sonsored by ayer Heallhcare lhal markels
hormonal female conlracelives Yaz and Mi-
rena, and vas suorled by an alliance of
1O inlernalional organizalions involved in
sexual heallh, including lhe Asia Iacihc
Council of Conlracelion. A free smarl hone
a, Iill Reminder Singaore, vas launched
by ayer lo mark lhe occasion for vomen lak-
ing lhe conlracelive ill. RK
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Snmc pcnp!c can carry
thc bactcrIa In thcIr thrnat
and rcmaIn asymptnmatIc

Si ngapor e Focus
October 2011
21
Radha Chitale
T
he Inslilule of Menlal
Heallh received lo honors
for lheir hosilal manage-
menl inilialives during lhe Asian
Hosilal Managemenl Avards
ceremony, held recenlly in Singa-
ore.
A anel of hosilal adminislra-
lion execulives from ma|or hosi-
lals around lhe vorld granled lhe
IMH lhe Grand Avard, vhich rec-
ognizes lhe hosilal vilh lhe mosl
number of nolable managemenl
ro|ecls submilled for consider-
alion, and vhich vas also a hnal-
isl in al leasl one of nine avard
calegories. The IMH also received
lhe grealesl informal recogni-
lion by lhe |udges, vilh six nods
among nine calegories.
Il's exhilaraling for me lo see
clinicians and execulives manage
lo come logelher and imrove
qualily of care, said IMH CL
Dr. Chua Hong Choon. This is
a big recognilion for us. and an
Elvira Manzano
T
he encouraging resulls of lhree
ma|or lrials on nev oral anlico-
agulanls aixaban, rivaroxaban
and dabigalran drev osilive
resonses from leading cardiolo-
gisls across lhe vorld, including
from Singaore, vho described
lhis develomenl as an exciling
nev era of lrealmenl allernalives
for lhrombolic disorders.
Seldom does lhis haen, mul-
lile drugs by differenl comanies
all of vhich have been shovn lo be
effeclive, said Dr. Mark Chan, as-
sislanl rofessor of medicine al lhe
Nalional Universily of Singaore
and consullanl cardiologisl al lhe
Nalional Universily Hearl Cenlre,
Singaore. This rovides more
diversily in lerms of lrealmenl o-
lions. Whelher lhis vould bring
dovn lhe cosl of lhe drugs lhrough
comelilion remains lo be seen,
hovever, he said.
Ior many years, lhe slandard
lrealmenl for lhrombosis and em-
bolism vas varfarin. In 2OO6, an-
olher oral agenl, ximelagalran,
almosl came inlo lhe markel, bul
vas ulled oul due lo liver loxicily,
said Dr. Chee Yen Lin, consullanl
hemalologisl al lhe Nalional Uni-
versily Cancer Inslilule, Singaore.
This has nol been a roblem vilh
lhese lhree nev drugs.
Rivaroxaban, aixaban and
dabigalran snalched lhe sollighl
from varfarin al lhe 2O11 Luroean
Sociely of Cardiology meeling.
In lhe RCKLT-AI* lrial, rivar-
oxaban vas found lo be as effeclive
as varfarin in alienls vilh alrial
hbrillalion, vilh an added benehl
of reduced falal bleeding.
The RL-LY** lrial for dabiga-
lran shoved lhal lhe drug reduced
lhe risk of slroke vilhoul increas-
ing lhe risk of ma|or bleeding as
comared lo varfarin.
In lhe ARISTTLL*** lrial, alri-
al hbrillalion alienls lrealed vilh
aixaban had fever slrokes or em-
bolic evenls lhan alienls lrealed
vilh varfarin, vilh fever ma|or
bleeding evenls, including fever
hemorrhagic slrokes.
Medical observers said lhis
could be lhe end of lhe road for
lhe noloriously lricky varfarin,
vhich is difhcull lo modulale. The
drug has a very narrov lheraeu-
lic range (Inlernalional Normal-
ized Ralio |INR jof 2 lo 3) and if ils
aclivily is nol checked regularly,
il can lrigger severe bleeding ei-
sodes, lhe mosl serious of vhich
can haen in lhe brain.
Clearly, lhal's lhe vorsl kind
of bleeding you vould fear. Wilh
lhese nev drugs, lhere vas less in-
lracranial hemorrhage. The effecl
is also more rediclable, lhus your
chances of falling vilhin a desired
lheraeulic range are higher lhan
vhen you are laking varfarin.
So lhere's a convenience faclor
lhere. You von'l need a secial-
isl lo monilor lhe alienl. Neilher
is lhere a need for dielary reslric-
lions and lifeslyle counseling.
Thus, il facililales lrealmenl even
in lhe rimary care level, Chan
concluded.
Chan and Chee vere co-
chairmen of lhe lvo-day Anli-
lhrombolic Iharmacolheraeulics
Symosium held al lhe Nalional
Universily Hosilal, Singaore
lasl monlh vhich gave doclors,
nurses and harmacisls insighls
inlo lhe lalesl harmacological
managemenl of venous and arle-
rial lhrombosis. The evenl also ad-
dressed some of lhe uncerlainlies
in lhe use of lhese nev drugs.

`ROCK|1-A|. Ritcrcxc|cn-cncc
!ci|q, crc|, !ircci jccicr Xc inni|iiicn
ccmpcrc! uiin tiicmin K cnicgcnism jcr
prctcniicn cj sirckc cn! |m|c|ism 1ric|
in Airic| |i|ri||ciicn
``R|-IY. Rcn!cmizc! |tc|uciicn cj
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in sirckc cn! cincr 1nrcm|ccm|cIic
ctcnis in ciric| |ri||ciicn
lMH wins Grand Award in hospita|
management
New era of treatment
a|ternatives to warfarin
endorsemenl lhal vhal ve're do-
ing is righl.
In addilion lo lhe Grand
Avard, lhe IMH von a calegory
avard for lhe besl 'Service Im-
rovemenl for Inlernal Cuslomers
Iro|ecl,' vilh lheir rogram lo im-
rove case managemenl and oul-
alienl follov u care for schizo-
hrenic and delusional alienls
lhal resulled in imrovemenl in
comliance from 78 ercenl al
baseline lo 88 ercenl.
Iour olher Singaorean hosi-
lals von calegory avards.
Singaore General Hosilal
vas named lhe vinner for lhe 'Hu-
man Resource Develomenl Iro|-
ecl' calegory vilh lheir slaff devel-
omenl inilialive called uilding
RIDGLS, Slrenglhening lies.
Khoo Teck Iual Hosilal von
in lhe 'Markeling, IR or Iromo-
lional Iro|ecl' calegory for lheir
in-house rehab relail slore, vhich
lhe |udges said broughl in revenue
for lhe hosilal and romoled el-
der heallh and indeendence.
Nalional Universily Hosilal's
rogram lo imrove alienl safely
and care coordinalion in lheir Re-
nal Unil von in lhe 'Ialienl Safely
Iro|ecl' calegory.
Changi General Hosilal had
lhe besl 'io Medical Lquimenl1
Iacililies Imrovemenl Iro|ecl'
vilh lheir inilialive lo imrove
vorkov vhen moniloring inlra-
cranial ressure.
This is a real innovalion lhal
has been lesled by economic anal-
ysis. vilh lhe ossibilily of reli-
calion, lhe calegory |udges said.
The AHMA |udging anel re-
ceived 315 ro|ecl enlries from
hosilals in 11 counlries. Iinalisls
vere recognized vilh excellence
avards if lhey did nol receive a
calegory avard.
Dr. Cnuc Hcng Cnccn, |MH C|O, ccccpis inc Grcn! Aucr! ci inc Asicn
Hcspiic| Mcncgcmcni Aucr!s ccrcmcnq.
Where can I
nd specic
information
on this drug?
Look up
MIMS Annual
or click in
MIMS.com
THE COMPLETE SOLUTION
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Sponsored Symposium Highlights
Sarcopenia refers to the involuntary loss of skeletal muscle mass that occurs with
advancing age due to a combination of several factors such as inadequate diet and
muscle disuse. Active measures for the treatment of this condition are essential, as
sarcopenia is linked to functional impairment, disability, falls and loss of independence,
thus having a detrimental impact on the overall quality of life of elderly patients.
1-3

The risk factors for sarcopenia include genetic susceptibility, female gender, low birth
rate, malnutrition, low protein intake, alcohol abuse, smoking, physical inactivity,
starvation, bed rest, immobility or de-conditioning and weightlessness. Other age-
related factors that contribute to the development of sarcopenia include increased
muscle turnover and protein degradation, decreased protein synthesis and reduced
number of muscle cells, as a result of increased myostatin and apoptosis. Hormonal
deregulation resulting in reduced testosterone, DHEA, oestrogen, 1-25 (OH)
2

vitamin D, growth hormone and IGF-1 levels and increased thyroid function and
insulin resistance further contributes to the pathogenesis of sarcopenia. In addition,
changes in the nervous system resulting in diminished central nervous system input
and neuromuscular disjunction along with mitochondrial dysfunction and reduced
UJWNUMJWFQ[FXHZQFWT\FQXTWJXZQYNSRZXHQJRFXXIJHQNSJ
4,5

Geriatric syndrome
9MJSJ\IJSNYNTSG^YMJ*ZWTUJFS<TWPNSL,WTZUTS8FWHTUJSNFNS4QIJW5JTUQJ
considers sarcopenia as a syndrome characterised by progressive and generalised
loss of skeletal muscle mass and strength and/or function with a risk of adverse
outcomes, such as physical disability, poor quality of life and death.
4
This is in
HTSYWFXYYTYMJJFWQNJWIJSNYNTSKTHZXXJITSQ^TSRZXHQJRFXXFSIXYWJSLYMIJHQNSJ
leading to functional impairment, disability, falls and loss of independence. Sarcopenia
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NS[TQ[JX HWTXXTWLFSX^XYJR UFYMTQTLNJX NS YMJ JQIJWQ^ FSI ITJX STY Y NSYT FS^
particular disease category, although associated with a number of comorbidities and
contributes to the deterioration in quality of life.
6
Low muscle mass, coupled low muscle strength and/or physical performance are the
WJVZNXNYJ HWNYJWNF YT JXYFGQNXM F INFLSTXNX TK XFWHTUJSNF .Y HFS GJ KZWYMJW HQFXXNJI
into three stages that may help in guiding clinical management of the condition.
These stages include pre-sarcopenia (reduced muscle mass), sarcopenia (reduced
muscle mass, along with reduced muscle strength or physical performance) and
severe sarcopenia (reduced muscle mass and strength and physical performance).
4
In clinical practice, various tools are available for the diagnosis and staging of
sarcopenia, such as:
4
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)*=&
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when there is no other apparent cause except ageing, or secondary, when sarcopenia
is due to poor nutrition, lack of activity or disease.
4
Nutrition-related sarcopenia
results from inadequate dietary intake of energy and/or protein. This may occur due
to poor intake, malabsorption, gastrointestinal disorders or use of medications that
cause anorexia. Activity-related sarcopenia develops as a result of prolonged bed
rest, sedentary lifestyle, deconditioning or zero-gravity conditions; while disease-
related sarcopenia is usually associated with advanced organ failure (heart, lung,
QN[JWPNISJ^TWGWFNSNSFRRFYTW^INXJFXJRFQNLSFSH^TWJSITHWNSJINXJFXJ
4
Body Composition and Ageing
Involuntary degenerative loss of skeletal muscle mass and function occurs at the rate
of 1-2% per year after the age of 30 years and accelerates with advancing age.
7
As
a result of ageing-associated loss of skeletal muscle mass, 53% of men and 68% of
women in the 60 to 69 year age group have sarcopenia. The process is accelerated
NSUFYNJSYX\NYMHFSHJWTWHMWTSNHNSFRRFYTW^INXJFXJX
Loss of skeletal muscle mass is postulated to be a major factor in the decline of muscle strength with time. This can severely impact the
overall quality of life in the elderly. Targeted nutritional intervention to prevent age-associated loss of lean body mass was the key topic of
INXHZXXNTSFYFQZSHMX^RUTXNZRIZWNSLYMJ=.&XNFS(TSLWJXXTK3ZYWNYNTSMJQIFY8NSLFUTWJNS/ZQ^&YYMJX^RUTXNZR5WTK/JFS
5NJWWJ2NHMJQ5WTKJXXTWTK2JINHNSJFSI-JFITKYMJ,JWNFYWNH8JW[NHJ,JSJ[F:SN[JWXNY^FQJFINSLJ]UJWYNSYMJJQIINXHZXXJIUWTRNXNSL
YWJFYRJSYTUYNTSXYMFYMF[JIJRTSXYWFYJIJKHFH^NSWJ[JWXNSLYMNXHTSINYNTS
Sponsored as a service to the medical profession by Abbott Laboratories.
*INYTWNFQIJ[JQTURJSYG^:'22JINHF9MJTUNSNTSXJ]UWJXXJINSYMNXUZGQNHFYNTSFWJSTYSJHJXXFWNQ^YMTXJTKYMJJINYTW
publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed.
:'22JINHF&QQWNLMYXWJXJW[JI3TUFWYTKYMNXUZGQNHFYNTSRF^GJWJUWTIZHJIG^FS^UWTHJXXNSFS^QFSLZFLJ
without the written permission of the publisher.
UBM Medica Asia Pte Ltd
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9JQ+F]*RFNQJSVZNW^XL%ZGRRJINHFHTR<JGXNYJ\\\ZGRRJINHFHTR
Summary
Sarcopenia or age-related loss of skeletal muscle mass results from a combination
of a number of individual factors. Sarcopenia may severely compromise the
independent functioning and overall quality of life of the elderly. However, the
condition is reversible with oral nutrition supplementation along with a structured
resistance training programme.
References
1.Rosenberg IH. Am J Clin Nutr. 1989;50:1231-1223. 2.Rosenberg IH. J Nutr88,TTIUFXYJW'-JYFQ/ Gerontol Med Sci. 2006;61A:1059-
(WZ_/JSYTKY&JYFQCurr Opin Clin Nutr Metab Care,WJJSQZSI1/JYFQMech Ageing Dev. 2003;124:287. 6.Inouye SK, et al. J Am Geriatr
Soc. 2007;55:780-791. 7.Timmerman KL, et al. Curr Opin Clin Nutr Metab Care 7NY_5JYFQClin Nutr. 2008; 27:740-746. 9.Thomas DR. Clin Nutr.
+NFYFWTSJ2&JYFQN Engl J Med(WNGG5/JYFQMed Sci Sports Exerc0FYXFSTX(8
et al. Am J Clin Nutr. 2005;82:1065-1073. 13.Paddon-Jones D, et al. Am J Physiol Endocrinol Metab. 2005;288:E761-767. 14.Rieu I, et al. J Physiol. 2006;575:305-315.
Figure 1: Oral nutritional supplement together with physical exercise increases
muscle strength
Figure 2: Stimulation of muscle protein synthesis requires higher essential amino
acid proportion in diet
Analysis of body composition of individuals in different age groups shows that
while ageing is associated with a gradual decline in body weight, body mass
index remains largely stable. However, ageing is marked with a steep drop in fat-
KWJJRFXX\NYMFHTSHZWWJSYXNLSNHFSYNSHWJFXJNSYMJUJWHJSYFLJTKGTI^KFY9MJ
body fat changes in aged adults is characterised by an increase in subcutaneous,
intermuscular, abdominal, epicardial and perivascular fat deposits.
8
Furthermore, the
weight-loss pattern of sarcopenia of ageing differs from that seen in cachexia or
TYMJWHTSINYNTSXXZHMFXFSTWJ]NFRFQFGXTWUYNTSTWM^UJWRJYFGTQNXR(FHMJ]NFNX
generally associated with advanced stages of various conditions or illnesses and is
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diminished food intake, while sarcopenia is generally ageing related and associated
with diet inadequacies, hormonal dysregulations and disuse of muscles due to bed
WJXYTWNSXZKHNJSYJ]JWHNXJ
9
Sarcopenia is reversible
Importantly, sarcopenia and the associated physical frailty are reversible with
appropriate intervention. Oral nutrition supplementation together with regular physical
exercise in the form of three 45-minute weekly sessions of resistance training over 10
\JJPXMFXIJRTSXYWFYJIXNLSNHFSYNRUWT[JRJSYNSRZXHQJXYWJSLYMNSFWFSITRN_JI
controlled trial that included 100 frail elderly patients with a mean age group of 87
years [Figure 1].
10
The ideal timing of protein intake is considered to be within one
hour of exercise.
11
Of note, stimulation of muscle protein synthesis may require a
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with higher proportion of certain essential amino acids is recommended in the elderly
[Figure 2].
12,13
In particular, oral protein supplementation with the amino acid leucine
has been found to increase protein synthesis in healthy elderly men as compared to
oral protein supplementation without leucine.
14
The Role of Oral Nutrition Supplementation in Reversing
Sarcopenia of Ageing
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(FS3ZYWNYNTS8YJRYMJ1TXXTK1JFS'TI^2FXX$
Prof. Jean-Pierre Michel
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Head of the Geriatric Service,
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Si ngapor e Focus
October 2011
23
New discovery may improve gastric
cancer therapy response
Elvira Manzano
S
ome lyes of gaslric can-
cer aear lo resond bel-
ler lo chemolheray lhan
olher lyes and may signihcanlly
redicl survival.
This is lhe key hnding of a
sludy by an inlernalional leam of
scienlisls led by researchers al lhe
Duke-Nalional Universily of Sin-
gaore (Duke-NUS).
Radha Chitale
T
he second inlerim resulls from
lhe ongoing large, observalion-
al GIDLN* sludy demonslraled
lhal lhe liver cancer drug sorafenib
is as safe lo use in cancer alienls
vilh imaired liver funclion as in
lhose vilh good liver funclion.
This roseclive sludy on a-
lienls vilh healocellular carcino-
ma (HCC) around lhe vorld, vhich
vas suorled by lhe harmaceu-
lical comany ayer HeallhCare
and resenled during lhe annual
meeling of lhe American Sociely
of Clinical ncology in Chicago,
Illinois, US in }une, is lhe largesl
observalional sludy on lhis alienl
oulalion lhus far.
HCC alienls from 37 counlries
vere enrolled in lhe GIDLN lrial
belveen }anuary 2OO9 and Decem-
ber 2O1O and 1,586 alienls receiv-
ing lrealmenl vilh lhe liver cancer
drug sorafenib vere folloved for 4
or more monlhs.
Trealmenl for HCC may vary
deending on hov imaired liver
funclion is, from cirrhosis, for ex-
amle. Ialienls vilh severely im-
aired, decomensaled livers may
nol benehl from lrealmenl. They
may also suffer more side effecls.
Sorafenib has roven efhcacy in
alienls vilh liver cancer and good
liver funclion. Ialienls vilh liver
cancer and somevhal imaired liv-
er funclion are offered cancer lreal-
menl, allhough dala on safely and
efhcacy in lhis oulalion is scarce.
Inlernalional guidelines do nol
recommend lrealmenl for alienls
vilh severely imaired liver func-
lion.
In lhe sludy, lrealmenl grou
A, vhich had excellenl liver func-
lion, included 965 alienls and
lrealmenl grou , vhich had im-
aired liver funclion, included 368
alienls.
Wilh drug-relaled adverse
evenls of all grades, lhe ercenlag-
es vere very, very similar belveen
lhe Child A and Child grous,
suggesling lhal alienls vilh liver
cancer and bad liver funclion can
lolerale sorafenib, vilh a safely
rohle almosl idenlical lo alienls
vilh liver cancer and good liver
funclion, said GIDLN invesliga-
lor Irofessor Riccardo Lencioni, di-
reclor of lhe Division of Diagnoslic
Imaging and Inlervenlion al Iisa
Universily Hosilal and School of
Medicine in Iisa, Ilaly.
Adverse evenls of any severily
occurred in 8O ercenl of grou A
alienls and 88 ercenl of grou
alienls. Drug-relaled adverse
evenls of any severily occurred in
66 ercenl of grou A alienls and
62 ercenl of grou alienls. Se-
vere drug-relaled adverse evenls
occurred in 28 ercenl of grou A
alienls and 54 ercenl of grou
alienls.
Grou did nol have a higher
incidence of blood-relaled adverse
evenls, lhough lhey did have a
higher incidence of liver-associal-
ed evenls. Hovever, lhe grou
oulalion began vilh oorer liver
funclion. Drug-relaled adverse
evenls vere similar and lhere vere
no unexecled adverse evenls in
grou .
Allhough lhe analysis shoved
similar safely rohle belveen
grous A and for sorafenib lher-
ay, alienls in grou slill have
oor life execlancy comared lo
grou A (5 monlhs vs. 1O monlhs).
Hovever, Lencioni noled lhal
individual alienls can vary and
lhose vho are slable and are nol de-
comensaling raidly may benehl
from sorafenib lrealmenl.
The A grou, of course, lhere is
no queslion, should be lrealed vilh
sorafenib, bul lhe grou is in lhe
middle he said. I'm nol suggesl-
ing all |liver cancer alienls vilh
imaired liver funclionj receive
sorafenib or any olher lheray.
Individual assessmenl of alienls
is very imorlanl and lhey are
somevhere in lhe middle. The
GIDLN dala shovs lhal if you are
lanning lo lreal lhal alienl vilh
sorafenib, you vill have a safely
rohle very similar lo a safely ro-
hle of a grou A.
`G|D|ON. G|c|c| |ntcsiigciicn cj
1ncrcpcuiic Dccisicns in Hcpciccc||u|cr
Ccrcincmc cn! cj iis 1rccimcni uiin
Scrcjcni|
5orafenib safe for |iver
cancer patients with
impaired |iver function
y analyzing lhe gene exres-
sion of 37 gaslric cancer cell lines,
lhe researchers vere able lo iden-
lify lvo dislincl sublyes of gas-
lric cancers - genomics inleslinal
(G-INT) and genomics diffuse
(G-DII). |Gcsirccnicrc|cgq 2O11,
141(2):476-485j
They lhen validaled lheir hnd-
ings in lumor samles from 521
gaslric cancer alienls and found
lhal alienls belonging lo lhe G-
INT sublye exhibiled signihcanl-
ly beller clinical oulcomes lhan
alienls belonging lo lhe G-DII
sublye.
This difference in survival re-
mains signihcanl even afler ad|usl-
ing for olher clinical sludy erim-
elers such as disease slage, said
Dr. Ialrick Tan, senior aulhor of lhe
sludy and associale rofessor in
lhe Cancer and Slem Cell iology
Research Irogram al Duke-NUS.
Thus, lhese sublyes carry lrue
rognoslic relevance.
Moreover, vhen lhe cell lines
vere lrealed vilh currenl chemo-
lheray agenls for gaslric cancer
5-uorouracil (5-IU), cislalin and
oxalilalin lhe G-INT cell lines
shoved signihcanlly beller re-
sonse lo 5-IU and oxalilalin, bul
vere more resislanl lo cislalin,
comared lo lhe G-DII cell lines.
ur sludy is lhe hrsl lo shov
lhal a roosed molecular classi-
hcalion of gaslric cancer can iden-
lify genomic sublyes lhal resond
differenlly lo lheraies, vhich
is crucial in efforls lo cuslomize
lrealmenls for alienls, Tan said.
Classihcalion of gaslric cancer
could move alienls from uniform
'one-size-hls all' rolocols lo er-
sonalized and olimized lrealmenl
slralegies.
Tan said a hase II sludy of
genomic-guided slandard of care
chemolheray in advanced gaslric
cancer alienls (3G) is nov under-
vay lo hnd oul if lailored lrealmenl
using genomic signalure imroves
resonse rale among alienls.
We hoe lo demonslrale lhal...
using our rediclive markers, ve
can achieve higher resonse rales
vilhoul lhe need of a lhree-drug
regimen, said Dr. Yong Wei Ieng,
lead invesligalor of lhe lrial and
senior consullanl al lhe Nalional
Universily Cancer Inslilule, Singa-
ore.
C|cssijqing gcncmic su|iqpcs cj
gcsiric ccnccr mcq nc|p ic cpiimizc
irccimcni sircicgics.
Sarcopenia is Reversible
Recommend Oral Nutritional
Supplementation and Exercise
$%%2TT/$%25$T25IE6(6)PTE/TD
1 Maritime Square, #12-01 HarbourFront Centre, Singapore 099253.
Tel: 6278 7366
References
1. A Cruz-Jentoft et al. Age Ageing. 2010;39:412-23. 2. Fiatarone MA et al. N Engl J Med. 1994;330:1769-1775. 3. AHA. Circulation. 2006 Jul 4;114(1):82-96.
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Oral nutrition supplementation associated with
physical exercises increases muscle strength.
2
Sarcopernia presents with a risk of adverse outcomes such as physical disability, poor quality of life and
death.
1
Currently, no medication has been proven to treat sarcopenia among healthy elderly. However, this
condition can be reversed with oral nutrition supplementation along with a structured resistance training
program.
2
P=0.001
Exercise Supplementaion Control Exercise &
Supplementaion
Change in muscle mass (%)
150
125
100
75
50
25
0
-25
Effects of oral nutrition supplementation and resistance training for 10
weeks on muscle strength in 100 frail elderly (mean age 87 years old).
Hip/knee extensor training
3 sessions (45 min) a week
360 kcal a day multinutrient supplementation
BMI ~ 25 kg/m
2
Loss of
Skeletal
Muscle Mass
Loss of
Muscle
Strength
Loss of
Function
Sarcopenia
1
+ =
OR
E
N
L
1
1
0
9
1
1
Si ngapor e Focus
October 2011
24
Radha Chitale
R
esearchers from Nanyang Technolog-
ical Universily (NTU) in Singaore
hoe lo idenlify a sel of 1O lo 15 bio-
markers lhal can redicl hearl disease vilh
more accuracy lhan before.
Wilh lhese nev biomarkers, in addilion
lo 13 knovn and validaled biomarkers, lead
researcher Assislanl Irofessor Nevman Sze,
of lhe Division of Slruclural iology and
iochemislry in lhe School of iological Sci-
ences al NTU, and colleagues said lhey vill
be able lo increase lhe rediclion caacily
for cardiovascular evenls and hearl disease
from 65 ercenl lo 8O ercenl.
The goal of hearl disease biomarkers is
lo idenlify al-risk alienls vell before lhey
become symlomalic and lreal lhem vilh a
ersonalized, revenlive aroach, lhe re-
searchers said.
Cardiac and vascular evenls accounled
for aboul 31.6 ercenl of lhe rincile causes
of dealh in Singaore in 2OO9, according lo
dala from lhe Minislry of Heallh.
In collaboralion vilh researchers from
lhe Nelherlands, Sze and colleagues lan lo
narrov a sel of more lhan 1OO candidale bio-
markers over one year dovn lo aboul 1O val-
idaled biomarkers using a high-lhroughul
syslem lhal delermines lhe frequency of a
single biomarker in a oulalion of alienls.
Aboul 2,OOO samles have been galhered
so far in lhis ongoing sludy, including sam-
les from aboul 8OO Singaoreans of Chi-
nese, Malay and Indian elhnicily.
The elhnically diverse samles should
hel clarify vhelher cerlain biomarkers are
more imorlanl for lhese oulalions com-
ared lo Caucasian oulalions, said Iro-
fessor Lee Chuen Neng, chair of lhe Univer-
sily Surgical Clusler al Nalional Universily
Heallh Syslems.
The researchers examined aorlic lissue
laken from alienls undergoing byass sur-
gery, as lhey assumed a high likelihood of
biomarkers in lhis localion. They also used
blood samles, bul blood may nol conlain all
lhe cardiovascular markers.
Lee said lhe samle lissue may have lim-
iled lheir oulcome because il did nol include
lhose vilh slroke or arrhylhmia or alhero-
sclerosis.
All arls of lhe lissue or blood samle
vere examined bul lhe researchers said lhere
vas a high likelihood of hnding biomarkers
in lhe glycoroleins involved in inlracellular
lransorl and signaling.
An evidence-based diagnoslic kil is slill
many years in lhe making, hovever, Lee
said.
The validaled biomarkers are nol cur-
renlly used lo redicl hearl disease because
lhe research surrounding lhem is slill re-
liminary. iomarkers are used rimarily in
cancer research.
There are also many olher faclors in-
volved in vhelher a erson develos hearl
disease and, righl nov, characlerislics such
as smoking, overveighl, high blood ressure
and family hislory of hearl disease can inler-
fere vilh a biomarker's rediclive value.
Rajesh Kumar
I
al around lhe hearl is more slrongly
linked lo alherosclerosis lhan eilher
body mass index (MI) or vaisl circumfer-
ence, according lo nev research.
While revious analyses have looked al
lhe relalionshi of ericardial fal lo alhero-
sclerosis in alienls vilh severe coronary
disease, lhe Mulli-Llhnic Sludy of Alhero-
sclerosis (MLSA) is lhe hrsl sludy lo hnd
such an associalion in heallhy, asymlom-
alic eole. |Rc!ic|cgq 2O11 Augusl. Lub
ahead of rinlj
The individuals in lhis sludy.did nol
have signihcanl coronary arlery narroving.
Desile lhis, lhey had coronary laque lhal
could be delecled by MRI, said senior au-
lhor Dr. David luemke, direclor of radiolo-
gy and imaging sciences al lhe Nalional In-
slilules of Heallh, elhesda, Maryland, US.
Ior lhe MLSA sludy, researchers recruil-
ed 183 individuals vilhoul clinical cardio-
vascular disease from held cenlers in alli-
more and Chicago 89 vomen and 94 men
vilh a mean age of 61 years. The sub|ecls
vere deemed lo be fairly reresenlalive
of lhe US oulalion, allhough mosl vere
overveighl, said luemke.
Magnelic resonance imaging (MRI) vas
used lo measure coronary arlery eccen-
lricily (ralio of maximal lo minimal arlery
vall lhickness) as a measure of early-slage
alherosclerosis and comuled lomograhy
(CT) vas used lo delermine ericardial fal
volume.
Iericardial fal is localed behind lhe
slernum, around lhe hearl, and ve can-
nol see il excel vilh CT or MRI, said
luemke. In some eole, exlra fal forms
referenlially in lhis area. We do nol knov
vhy. Hovever, exlra fal around lhe hearl is
generally associaled vilh being overveighl
or obese.
The resulls shoved lhal ericardial fal
volume correlaled signihcanlly vilh lhe de-
gree of laque eccenlricily in bolh men and
vomen. Afler ad|uslmenl for MI, vaisl
circumference, lradilional risk faclors, C-
reaclive rolein level and coronary calcium
conlenl, lhe relalionshi belveen ericar-
dial fal and laque eccenlricily remained
signihcanl in men, bul nol in vomen.
The hndings indicale yel anolher rea-
son lhal obesily is bad for us. arlicularly
vhen lhe fal forms around lhe hearl, since
lhe hearl fal aears lo furlher romole cor-
onary arlery laque, said luemke.
Singaoreans are gelling more obese, a
vorrying lrend lhal bolh governmenl and
heallh rofessionals are lrying lo curlail,
said Dr. Ielix Keng, senior cardiologisl al
lhe Nalional Hearl Cenlre Singaore, vhile
commenling on lhe sludy.
The hndings should serve as a reminder
lo all doclors lo convey lhe heallh hazards
of being fal lo lheir alienls. Hovever, lhe
sludy aulhors erformed bolh a cardiac
MRI and CT scans lo arrive al lhe conclu-
sion, vhich is nol raclical in clinical rac-
lice because of associaled cosls and side ef-
fecls, said Keng.
Moreover, lhe aulhors could nol shov
lhis relalionshi in vomen afler slalislical
correclion, bringing |cardiac CT and MRIj
use inlo furlher doubl.Il should be noled
lhal lhere is an increasing ulilizalion of
cardiac CT vorldvide, and erhas vhen
a alienl has a cardiac CT done for vhal-
ever reason, lhe inlerreler could also look
al ericardial fal as anolher fealure of coro-
nary arlery disease.
Predicting heart disease more accurate,
sti|| tricky
Pericardia| fat is ear|y sign of
heart disease
Si ngapor e Event s
19/10/11
GP-CME Care of Patients In Remission in Primary
Care Especially Colorectal Care
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
20/10/11
GP-CME Screening for Dementia and Cognitive
Impairment
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
25/10/11
GP-CME Food Allergy
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
27/10/11
GP-CME Managing Neck Lumps
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
1/11/11
GP-CME Polypharmacy
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
3/11/11
GP-CME Common Hepato Biliary Problems in
General Practice
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
4/11/11
GP-CME Update on management of PTB
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/
nhgeventsforhos/calendarofevents.
asp?eventgroup=4&
9/11/11
GP-CME Headaches seen in Primary Care - Red
Flags, Treatment and When to Refer
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
10/11/11
GP-CME Upper GI cancers. Warning Signs. How
they present and when to refer
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
12/11/11
Breast Cancer Survivorship Forum
Info: National Cancer Centre Singapore
Tel: +65 6225 5655
Website: www.nccs.com.sg
16/11/11
GP-CME Hepatitis B and Hepatitis C - diagnosis
and treatment
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
17/11/11
GP-CME Opthalmoplegia for the Family Physician
Info: National Healthcare Group (NHG) Polyclinics
Tel: +65 6355 3000
Website : www.netcare.com.sg/nhg/nhgeventsforhos/
calendarofevents.asp?eventgroup=4&
Icc! rcsccrcncr Assisicni Prcjcsscr Ncumcn Szc jrcm inc Ditisicn cj Siruciurc| Bic|cgq cn!
Biccncmisirq in N1Us Scncc| cj Bic|cgicc| Scicnccs.
Si ngapor e Focus
October 2011
25
Rajesh Kumar
U
lo 2O er cenl of alienls
may be vrongly diag-
nosed vilh hyerlension
based on lheir blood ressure (I)
readings in clinics, leading lo un-
necessary lrealmenl, according lo a
cardiologisl.
Some alienls may exerience
lhe 'vhile coal' effecl or 'vhile coal
hyerlension' |vhereinj lhey don'l
have hyerlension, yel lheir I is
high vhen measured al lhe doc-
lors' ofhce, ossibly due lo slress
or anxiely, said Dr. Slanley Chia,
a cardiologisl al lhe Nalional Hearl
Cenlre Singaore.
Chia vas commenling on a UK
sludy lhe resulls of vhich suggesl-
ed lhal ambulalory I readings
are lhe mosl cosl-effeclive vay
for diagnosing and lrealing hy-
erlension. |Icncci 2O11 Augusl 24
Lub ahead of rinl. DI:1O.1O161
SO14O-6736(11)61184-7j
Ambulalory moniloring con-
sisls of vearing a cuff allached lo
a orlable I measuring device for
24 hours, during vhich lhe device
measures I lyically half-hourly
during lhe day and hourly over-
nighl. The individual brings lhe
device back lhe folloving day lo
lhe clinic, vhere I recordings are
dovnloaded onlo a comuler and
an aulomalic reorl is generaled.
ecause I varies during lhe
day vilh a erson's differenl ac-
livilies, lhis allovs a more comre-
hensive iclure of an individual's
blood ressure. Long-lerm sludies
have shovn lhal lhe average blood
ressure over a 24 hour eriod is a
beller rediclor of adverse cardio-
vascular evenls lhan I measured
during a slandard clinic aoinl-
menl, said lhe researchers.
Allhough roviding such a I
measuring device may nol be feasi-
ble for Singaoreans vilh susecl-
ed hyerlension, Chia suggesled
lhal hysicians should inslead lake
reealed I readings over several
visils and include home I read-
ings, if ossible, before ulling
anyone on anlihyerlensive drugs.
This vould hel effeclively
manage lhose vho are al high-
er risk of fulure cardiovascular
evenls, vhile reducing lhe cosl of
unnecessary lrealmenl, he said.
In lhe UK sludy, lhe researchers
used a delailed malhemalical mod-
I
hysicians are loo readily re-
scribing choleslerol lover-
ing drugs such as slalins lo lhose
vilh borderline hyerliidemia,
ralher lhan laking lhe lime for a
more effeclive aroach involving
counseling on lifeslyle and diel,
according lo one exerl.
Singaoreans vilh moderalely
elevaled choleslerol should be en-
couraged lo include in lheir diel
secihc choleslerol lovering foods
such as soy, eas, beans, lenlils
and nuls before ulling lhem on
drugs, said Dr. }ack Tan, a cardiol-
ogisl al lhe Nalional Hearl Cenlre
Singaore.
Tan vas commenling on lhe
resulls of a recenl sludy vhich
shoved lhal such food ilems re-
duce LDL- choleslerol by u lo
13.8 ercenl vhen combined
vilh counseling. |jAMA 2O11,
3O6(8):831-839j
The Canadian sludy included
351 alienls vilh hyerliidemia
randomized lo receive eilher a
conlrol lov fal diel (vilh cereals,
fresh fruils and vegelables) or lov
fal diel vilh choleslerol lovering
foods and lvo counseling sessions
(called rouline dielary orlfolio)
or lhe same vilh 7 counseling ses-
sions ( inlensive dielary orlfolio)
over a eriod of 6 monlhs. Iarlici-
anls vere given measuring cus
and soons lo assisl in orlion
conlrol.
Dr David }enkins of Sl. Mi-
chael's Hosilal and lhe Uni-
versily of Toronlo, Canada, and
colleagues found lhe change in
baseline LDL-choleslerol levels
from lhe beginning of lhe sludy
lo veek 24 in lhe conlrol diel vas
-3.O ercenl (or -8 mg1dL). In lhe
rouline and inlensive dielary orl-
folio inlervenlions, lhe reseclive
changes vere -13.1 ercenl (-24
mg1dL) and -13.8 ercenl (-26
mg1dL).
|Thej reduclion vas associ-
aled vilh dielary adherence. We
believe lhis aroach has clinical
alicalion. A meaningful 13 er-
cenl LDL-C reduclion can be ob-
lained afler only lvo clinic visils
of aroximalely 6O-and 4O-min-
ule sessions, said lhe aulhors.
Ior alienls in lhe borderline
range, lhis simle lask is sufhcienl
bul lakes much more efforl. In
lhe long run, a roer diel lrans-
lales nol |usl lo beller choleslerol
conlrol bul likely has long lerm
melabolic imacl for body veighl,
diabeles and ossible cancer risk,
added Tan.
The role of counseling and con-
slanl moniloring of alienl's diel is
aclually very imorlanl. and GIs
have a big arl lo lay. RK
Repeat BP readings crucia| in
diagnosing hypertension
Push for specic dietary
changes before starting drugs
el lo eslimale lhe cosl-effecliveness
of lhree diagnoslic slralegies _re-
ealed I readings in clinic, home
I moniloring and ambulalory
moniloring vilh aulomalic device
- lo delermine lhe diagnosis of hy-
erlension, before concluding lhal
lhe ambulalory olion vas lhe
mosl cosl-effeclive.
As a resull of lhe above hnd-
ings, lhe UK's Nalional Inslilule
for Heallh and Clinical Lxcellence
(NICL), vhich heled fund lhe
sludy, is recommending ambu-
lalory moniloring as besl rac-
lice, as arl of guidelines |oinlly
devised vilh lhe rilish Sociely
of Hyerlension.
Addilional cosls from ambula-
lory moniloring can be offsel by
savings from beller largeled lreal-
menl, said lhe researchers.
While exlaining lhe sludy's
relevance lo Singaore, Chia cau-
lioned lhal lhe cosl savings vill
only be signihcanl if lhe cosls of
reeal clinic visils lo ascerlain lhe
accuracy of lhe diagnosis are high,
or if home I moniloring cannol be
achieved in an inexensive man-
ner.
Neverlheless, lhis sludy hels
us realize lhe imorlance of mak-
ing accurale diagnoses of hyer-
lension.
Scmc pciicnis mcq cxpcricncc inc
uniic ccci" cjjcci uncrcin incq
!cni nctc nqpcricnsicn, |ui incir
BP is nign uncn mccsurc! ci inc
!ccicrs cjcc.
Industry UPDATE
Industry Update
brings you updates on
disease management
and advances in
pharmacotherapy
based on reports from
symposia, conferences
and interviews as well
as the latest clinical
data. This months
Industry Update was
made possible through
unrestricted educational
grants from MSD.
Setting new standards for
preventing HPV-related
diseases Pg 26
Look up
MIMS
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drug listing
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this medicine
before or after
meals?
Guide to Symbols
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out Food
THE COMPLETE SOLUTION
100%
pure knowledge
H
PV may be a chronic life-
time infection with a long
period of latency. Even in
those with rst manifestation of
the disease, it can lay dormant and
return 20, 30 or even 50 years later
in the form of cancer.
The virus can have an incuba-
tion period of 1 to 8 months, af-
ter which active growth of warts
and lesions can be seen until the
immune response of the host.
Currently, there is no therapeutic
virucidal option against HPV and
treated lesions will keep coming
back until the patient mounts an
immune response to the infection.
Up to 20% of those infected
with HPV will end up getting a
chronic or recurrent disease.
The disease burden due to
both low- and high-risk HPV geno-
types is huge and growing.
Low-risk HPV genotypes 6 or
11 are responsible for 90 percent
of external genital warts and an
equally high percentage of la-
ryngeal papillomatosis in young
adults. Traditionally, laryngeal
papillomatosis was seen mainly in
infants due to suspected mother-
to-child transmission of infection
during vaginal birth.
HPV genotypes 6 and 11 are
also responsible for the two most
frequent abnormalities on a pap
smear: atypical squamous cells of
undetermined signicance (AS-
CUS) and low-grade cervical dis-
ease. Not knowing what type of
HPV a patient has, we should man-
age them as if they have high-risk
HPV precancerous lesions.
HPV on the rise in Singapore
The incidence of genital warts
in Singapore increased by 76 per-
cent between 2000 and 2010 (Fig-
ure). [National Skin Centre data on
le]
Although warts are the most
common manifestation of HPV
infection in men, there is actually
a wide variety of HPV-related dis-
ease in males. We are seeing more
and more recurrent respiratory
papillomatosis, penile intraepithe-
lial neoplasia (PIN) and carcinoma,
anal intraepithelial neoplasia (AIN)
and carcinoma and some oropha-
ryngeal cancers (of the tongue,
tonsils, throat, and soft palate) in
men.
HPV genotypes 16 and 18 are
the deadliest
HPV is present in 100 percent
of cervical cancers, of which high-
risk genotypes 16 and 18 are re-
sponsible for a vast majority of
squamous cell cancers and adeno-
carcinomas. HPV 16 is mostly im-
plicated in 90 percent of the anal
cancer cases and half the cases of
vulvar and vaginal cancers.
More worrying is the fact that
once a patient is diagnosed with
one HPV-related cancer, they are
at increased risk of getting anoth-
er. According to the Surveillance,
Epidemiology, and End-Results
(SEER) program of the National
Cancer Institute in the US, those
with a diagnosis of cervical, anal,
vulvar or vaginal cancers were at
high risk of subsequently develop-
ing cancer of the pharynx, larynx,
tongue or tonsils in their lifetime.
Women also remain at high
risk of acquiring HPV infection
throughout their lifetime. [J Infect
Dis 2004; 190:2077-87]. As they
grow older, they are likely to have
mature partners who are more
sexually experienced and are likely
to be infected with HPV. They can
pass it on to them.
Recent data now suggest that
HPV vaccines are eective in non-
adolescent older adults. The quad-
rivalent HPV vaccine (Gardasil;
Merck Sharp & Dohme), when test-
ed in women between the ages of
26 and 45, showed a high level of
ecacy against persistent infec-
tions, carcinogenic lesions and
warts (Table).
A long-term study of quadriva-
lent HPV vaccine in Nordic coun-
tries suggests protection for up to
7.5 years after vaccination.
The real-life impact of vaccina-
tion of Australian men and women
with quadrivalent HPV vaccine
also showed a marked drop in
the cases of genital warts in both
sexes.
Why vaccinate men?
HPV-related diseases aect
both men and women. Data from
the US suggest the burden of HPV-
related cancers in men is equal to
that of cervical cancer in women.
The 2008 gures show 11,070
cases of new HPV-related cervi-
cal cancer were diagnosed in the
country in that year, whereas the
cases of the cancers of the oral
cavity, pharynx, anal canal and pe-
nis caused by HPV were between
8,696 and 11,228.
Is it ethical, therefore, that
Setting new standards for preventing HPV-related diseases
Human papillomavirus (HPV) is the most common sexually transmitted virus that is responsible not only for genital warts and cer-
vical cancer, but also for anal, vulvo-vaginal, penile and oropharyngeal cancers. At a recent symposium supported by Merck Sharp
& Dohme and held in conjuction with the 8th Singapore International Congress of Obstetrics and Gynaecology, Dr. Marc Steben,
a family physician from Quebecs National Public Institute in Montral, Canada, highlighted the burden of disease beyond cervical
cancer, while building a case for vaccinating both boys and girls against HPV.
Dr Marc Steben
Family physician, Quebecs National Public Institute in
Montral, Canada
Type of infection Ecacy (%) 95% CI
HPV6/11/16/18 Persistent infection,
CIN or EGL
88.7 78.1 94.8
Persistent infection 89.6 79.3 95.4
CIN (any grade) 94.1 62.5 99.9
CIN 2/3 worse 80.0 0 99.6
EGL 100 30.8 100
Condyloma acuminatum 100 30.8 100
VIN 2/3 or VaIN 2/3 n/a n/a
*Ferris, DG for the FUTURE III Steering Committee, EUROGIN 2010
CIN: cervical intraepithelial neoplasia; EGL: external genital lesions;
VIN: vulvar intraepithelial neoplasia
Table. Quadrivalent HPV vaccine efective in women 26-45 years of age.* 1400
1200
1000
800
600
400
200
0
Male Female Total
77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07 09
Year
N
o
.

o
f

c
a
s
e
s
Figure. Genital warts in Singapore
men are not able to benet from
HPV vaccination? Is it ethical that
women are expected to be the
ones who bear the burden of HPV
prevention? One study which
evaluated the ecacy of quadri-
valent HPV vaccine in men showed
it results in reduction not just in
genital warts, but also in anal pre-
cancerous lesions. Therefore, vac-
cination of men, younger men in
particular, should be considered
important.
Vaccinating women alone
leaves a large pool for circulation
of HPV 6 and 11 in men. Vaccinat-
ing men would reduce the HPV
disease burden in both men and
women.
We need to remember that
HPV transmission can occur even
with a single partner, if the part-
ner was sexually involved prior to
getting into a monogamous rela-
tionship. Therefore, being married
or in a long-term monogamous
relationship is not an insurance
against HPV.
Gender neutral vaccination,
therefore, should be the norm. His-
tory tells us that selective vaccina-
tion cannot be eective. Take the
case of rubella vaccine. It is given
primarily to prevent neonatal ru-
bella complications arising from
acquiring rubella during the fetal
organogenesis period in pregnan-
cy. Since only women can transmit
rubella to their fetus in utero, the
initial argument was why vac-
cinate men? The neonatal rubella
syndrome continued because of
this inadequate strategy.
Besides, there are limits of pri-
mary prevention outside of a pre-
ventive vaccine such as the quad-
rivalent HPV vaccine. Abstinence
can protect against HPV transmis-
sion, but only while it lasts. Most
human beings will become sexual-
ly active at some stage and be ex-
posed to HPV. Condoms are good,
but far from perfect.
A question of equity
Vaccinating men is also a ques-
tion of equity. If a disease exists
in both sexes, they should have
the same treatment. Of course,
the manifestation of HPV-related
diseases is dierent between men
and women. But prevention looks
almost as good for men as it does
for women.
The knowledge about HPV-
related cancers in men is still in its
nascent stage. But we now know
much more than we did. Therefore,
I think there is going to be a strong
push for HPV vaccination for men.
Many countries are already look-
ing at adding men to their HPV
vaccination program.
Lessons for GPs
In all this, physicians need to
remember that their recommen-
dation is the most important rea-
son why a patient accepts vaccina-
tion.
An HPV vaccine has no e-
cacy when it is lying in the fridge.
HPV vaccination may be the best
way to ght the inequities about
womens health issues. Physicians
should lead by example and vac-
cinate both their sons and daugh-
ters.
Sexual health is very much
part of the overall health of a
person. Physicians should always
include questions about their pa-
tients sexual health when consult-
ing. Those who are in appropriate
age bracket should be counseled
about HPV infection and oered
the vaccine.
Nobody is naturally immune
against HPV infection. It is a huge
and growing burden. People are
marrying late, having pre marital
sex and divorce rates are high.
Right now, vaccination is our rst
line of defense against HPV.
I ndust r y Updat e 26
News
October 2011
3LVUHYK@HW
R
ecenl advancemenls in ra-
diolheray have imroved
lhe lrealmenl oulcome for
alienls vilh head and neck can-
cers, says an exerl.
Inlensily-modulaled radia-
lion lheray (IMRT), image-guid-
ed radialion lheray (IGRT) and
volumelric-modulaled radialion
lheray (VMAT) imrove head
and neck cancer radiolheray
lrealmenl oulcomes and alienls'
qualily of life, said Irofessor
}ason Cheng Chia-Hsien, of lhe
Division of Radialion ncology,
Nalional Taivan Universily Hos-
ilal, Taiei, Taivan.
IMRT greally imroves a-
lienls' qualily of life by accuralely
largeling recise amounls of ra-
dialion lo lhe affecled area, avoid-
ing unnecessary exosure of lhe
arolid glands and, lherefore, re-
serving saliva roduclion. |j C|in
Oncc| 2OO7,25(31):4873-9j
IMRT used in con|unclion vilh
IGRT and VMAT ensures inoinl
accuracy of radiolheray and a
signihcanl reduclion in lrealmenl
lime, he said. In addilion lo im-
roving alienls' qualily of life,
lhese lechnologies require less
lrealmenl lime, vhich lranslales
inlo lhe abilily lo lreal more a-
lienls er day, he added.
In IMRT, very small beams of
radialion are largeled al a lumor
from many angles. The radialion
inlensily and beam shae are
conlrolled and ad|usled mullile
limes lo accommodale lhe shae
of lhe lumor.
This resulls in accurale o-
silioning of lhe radialion beam
and reserving heallhy lissue.
Conlrol of lhe radialion beam is
fully managed by comulers and
slale-of-lhe-arl soflvare. |Inlensi-
ly Modulaled Radialion Theray
verviev. uuu.naocIlnlc.org/
lnrI/houlIuorks.hInI Accessed
on 19 Auguslj
Ior IGRT, high-qualily lhree-
dimensional images are derived
from comuled lomograhy (CT)
scans and used lo inoinl lumor
siles. IGRT allovs lhe ad|uslmenl
of a alienl's osilion during lreal-
menl lo ermil furlher largeling
recision. Higher recision allovs
lhe ossibilily of using a higher
radialion dosage delivered lo can-
cer cells, ensuring lhe deslruclion
of cancer cells. |Image-Guided Ra-
dialion Theray verviev. uuu.
naocIlnlc.org/lgrI/ Accessed on
19 Auguslj
VMAT is a furlher enhance-
menl of IMRT, ulilizing arcs of ra-
dialion lheray inslead of lhe con-
venlional beam. VMAT reduces
lrealmenl lime and is arlicularly
useful vilh alienls vho require
regular radiolheray. |Tyes of
radialion lheray. uuu.nao-
cIlnlc.org/radlaIlon-oncoIog-rsI/
dlseases.hInI Accessed on 19 Au-
guslj
Cheng vas seaking al Ianlai
Hosilal Kuala Lumur's Head
and Neck Cancer Symosium re-
cenlly.
Advancements in radiotherapy improve
treatment of head & neck cancers
Prccisc rc!iciicn cxpcsurc is kcq in
icrgciing ccnccrs cj inc ncc! cn!
ncck.

In addItInn
tn ImprnvIng
patIcnts' qua!Ity
nI !IIc, thcsc
tcchnn!ngIcs rcquIrc
!css trcatmcnt tImc
27
Nagging their way to get what they want
More evidence on the benets
of sh oi| supp|ementation
Picking the right drug for
acute manic episodes
7HUR1P[:PU
I
arenls aren'l lhe only ones doing lhe
nagging novadays, as revealed by a
nev sludy.
Researchers al lhe }ohns Hokins loom-
berg School of Iublic Heallh ublished a
sludy on lhe 'Nag Iaclor' in lhe recenl Augusl
2O11 issue of jcurnc| cj Cni|!rcn cn! Mc!ic.
The 'Nag Iaclor' refers lo young children's
lendency lo relenllessly nag lheir arenls lo
acquire ilems due lo adverlising and markel-
ing inuences.
Thc thrcc nags
orzekovski and co-researchers discovered
lhal nagging fell inlo lhree calegories |u-
venile nagging, maniulalive nagging and
nagging lo lesl boundaries. Ior lhese lhree
lyes of nagging, lhe molhers ciled 1O vays
of dealing vilh lheir children yelling, ig-
noring, dislracling, slaying calm and consis-
lenl, avoiding lhe commercial environmenl,
negolialing and selling rules, alloving al-
lernalive ilems, exlaining lhe reasoning
behind lhe choices and limiling commercial
exosure.
Maniulalive and overall nagging in-
creased as lhe child aged, and vhen il came
lo dealing vilh lhe child's nagging, lhe mosl
common melhods lhal molhers used vere
exlaining lo lhe children lhe reasons behind
making or nol making cerlain urchases (35
ercenl of lhe lime), vhile 36 ercenl sug-
gesled limiling commercial exosure lo lheir
children. There vas also a general consen-
sus lhal giving in lo lhe child vas one of
lhe leasl effeclive slralegies. Senior aulhor
of lhe sludy, Dina orzekovski (LdD, LdM,
MA), of lhe loomberg School's dearlmenl
of heallh, behavior and sociely, said lhere is
increasing focus on lhe markeling and con-
sumlion of |unk food in lighl of lhe child-
hood obesily eidemic.
Lven lhough children are nol lhe rima-
ry shoers in a arlicular household, said
orzekovski, child-orienled, lov-nulrilion
foods and drinks (|unk foods) are being as-
similaled inlo lhe households and diels of
young children lhrough adverlising.
The sludy discovered lhal even if lhe fre-
quency of media use (eg, frequency of valch-
ing lelevision) vas lov, a child's familiarily
vilh a commercial lelevision characler sig-
nihcanlly correlaled vilh overall and secihc
lyes of nagging. According lo lhe sludy,
molhers also lisled ackaging, characlers and
commercials as being ma|or faclors comel-
ling lheir children lo nag.
A lolal of 64 molhers vilh children aged 3
lo 5 years vere inlervieved on loics such as
household environmenl, child's demograh-
ics, media use, ealing and shoing raclices,
and lheir child's requesl for adverlised ilems.
Molhers vere inlervieved because lhey are
lradilionally regarded as, and mosl likely lo
be, nulrilional galekeeers of lhe household
diel. Addilionally, molhers are more likely lo
conlrol food urchasing and lhe rearalion
of food for small children.
orzekovski concluded lhal in order lo
address childhood obesily, lhere may be a
need lo limil lhe amounl of food and bever-
age adverlisemenls in lhe mass media, as lhis
vould ullimalely lead lo a lessening of chil-
dren's nagging for unheallhy foods.
I
osilive hndings on lhe use of hsh oil
sulemenlalion in cognilive funclion-
ing and brain slruclure have recenlly come
lo lighl.
A sludy by Rhode Island Hosilal's Al-
zheimer's Disease (AD) and Memory Disor-
ders Cenler, US, found osilive associalions
belveen lhose vho look hsh oil sulemenls
and cognilive funclioning comared lo lhose
vho did nol lake lhe sulemenl.
Hovever il is vorlhvhile noling lhal lhe
osilive associalion vas only signihcanl in
lhose individuals vho had a normal baseline
cognilive funclion and in lhose vho vere
negalive for genelic risk faclors for AD (lhe
AIL4 gene).
According lo lead researcher Lori Daiello
(Iharm.D), lhe hndings suggesl a ossible
benehl of hsh oil sulemenlalion on brain
heallh and aging.
The resulls of lhe sludy vere reorled al
lhe Inlernalional Conference on Alzheimer's
Disease, held in Iaris, Irance, recenlly.
A lolal of 819 individuals vere included
in lhe sludy, vhich ulilized dala from lhe
Alzheimer's Disease Neuroimaging Inilia-
live (ADNI). ADNI is a US Nalional Insli-
lules of Heallh (NIH)-funded, mullicenler
sludy vhich folloved older adulls vilh nor-
mal cognilion, mild cognilive imairmenl
and lhose vilh Alzheimer's disease (AD)
for 3 years. The sub|ecls undervenl eriodic
memory lesling and brain magnelic reso-
nance imaging (MRIs).
The dala vere lhen analyzed lo comare
cognilive funclioning and brain alrohy in
alienls vho sulemenled vilh hsh oil ver-
sus lhose vho did nol use hsh oil al all.
Il vas discovered lhal lhose laking hsh
oil sulemenls had beller cognilive func-
lioning comared lo lhose vho did nol lake
sulemenls. A unique hnding reorled by
lhe researchers vas lhe clear associalion be-
lveen hsh oil sulemenlalion and brain
volume lhis meanl lhal lhose using hsh oil
exerienced less brain shrinkage comared
lo lhose vho did nol use il. Again, lhis vas
only signihcanl in lhose vilhoul lhe genelic
risk for AD.
Daiello said lhe observalions should
serve as a basis for furlher sludies on lhe
ossible effecls of long-lerm hsh oil sule-
menlalion on markers of cognilive decline
and also on lhe olenlial inuence of genel-
ics on lhese oulcomes. P]S
3LVUHYK@HW
A
nlisycholics have been shovn lo be
more effeclive lhan mood slabilizers
in lackling acule manic eisodes, accord-
ing lo a nev sludy.
A sludy ublished in 1nc Icncci found
lhal lhe anlisycholics haloeridol, ris-
eridone and olanzaine did beller lhan
mood slabilizers.
Currenl guidelines do nol differenli-
ale belveen lhe lvo classes of drugs, said
sludy aulhors Dr. Andrea Ciriani, of lhe
dearlmenl of ublic heallh and commu-
nily medicine, Seclion of Isychialry and
Clinical Isychology, Universily of Verona,
Ilaly, and Irofessor }ohn Geddes, of lhe
dearlmenl of sychialry, Universily of
xford, UK. |Icncci 2O11 DI:1O.1O161
SO14O-6736(11)6O873-8j
The aulhors dehned mania as an ex-
cessively raised mood lhal affecls aboul
1 ercenl of lhe oulalion.
The lendency lo cycle belveen bouls
of mania and deression dehnes lhe diag-
nosis of biolar disorder.
Ciriani and colleagues examined lhe
resulls of 68 randomized conlrolled lri-
als (16,O73 arlicianls) from 198O lo 2O1O,
vhich comared lhe mosl common drugs
used lo lreal acule mania in adulls. Il vas
discovered lhal haloeridol, olanzaine and
riseridone vere lhe mosl effeclive drugs.
The aulhors found lhal haloeridol
had lhe highesl number of signihcanl
differences in head-lo-head comarisons
vilh mood-slabilizing drugs, and vas
more efhcacious lhan ariirazole, ase-
naine, carbamazeine, valroale, gaba-
enlin, lamolrigine, lilhium, queliaine,
loiramale and zirasidone. In addilion,
riseridone, olanzaine and queliaine
vere more likely lo resull in alienl com-
liance and vere seen lo be beller lhan
many mood slabilizers, such as lilhium,
lamolrigine, loiramale and gabaenlin.
They concluded lhal lhe resulls emha-
size lhe need for nev lrealmenls lo shov ei-
lher grealer efhcacy or accelabilily lhan lhe
exisling besl slandard lrealmenls. The dala
from lhis sludy could rove lo be ivolal in
develoing clinical raclice guidelines on
handling acule manic eisodes, lhey added.
The aulhors, hovever, caulioned lhal,
All slalemenls comaring lhe merils of
one medicine vilh anolher musl be lem-
ered by lhe olenlial biases and uncer-
lainlies lhal resull from choice of dose and
choice of alienls.
|tcn cni|!rcn ccn ncg ic gci unci incq ucni.
|isn ci| ccnsumpiicn |cc!s ic |css |rcin
snrinkcgc.
Hc|cpcri!c| jcun! ic |c mcsi cjjcciitc in ccuic
mcnic.
Thc nbscrvatInns
shnu!d scrvc as a basIs
Inr Iurthcr studIcs

News
October 2011
28
3LVUHYK@HW
A
clear, all-encomassing
dehnilion of non-allergic
aslhma and vhal lriggers
il remain elusive and oorly un-
derslood, says an exerl.
Non-allergic aslhma, also
knovn as inlrinsic aslhma, is lrig-
gered by faclors nol relaled lo aller-
gies. Il is characlerized by airvay
conslriclion and inammalion,
vilh symloms vhich are generally
similar lo allergic aslhma. The dis-
linclion belveen allergic and non-
allergic aslhma is lhal lhere is no
immune syslem involvemenl in lhe
laller. |Non-allergic Aslhma, uuu.
ccjc.crg/!isp|cq.cjm?i!=8csu|=17
Accessed on 25 Auguslj
Any number of relalively be-
nign lriggers can cause a non-aller-
gic aslhma eisode, said Dr. Ihili
}. Thomson, Winlhro Irofessor
of Resiralory Medicine al lhe Uni-
versily of Weslern Auslralia and
medical direclor of lhe Lung Insli-
lule of Weslern Auslralia.
Lxercise, exosure lo cold air
and slress as vell as reux can lrig-
ger aslhma. Consuming medica-
lions like asirin and NSAIDs, and
vine and food addilives can also
lrigger aslhma, he oinled oul.
Lnvironmenlal ollulanls like ex-
hausl fumes, cigarelle smoke and
isocyanales from ainls are knovn
lo lrigger aslhma allacks in some
alienls, he added. Ialienls can
also have hxed airvay obslruclion
and have aslhma lhal redomi-
nanlly affecls lhe smaller airvays
of lhe lung.
Thomson suggesled doclors
lake a delailed alienl hislory and
use a more rigorous aslhma inves-
ligalion using ov-volume loo,
skin lesling, exhaled nilric oxide
(eN) lesling, immunoglobulin L
(IgL) lesling and rescribe secihc
lheray for non-allergic aslhma.
He emhasized lhal lrealmenls
such as cromoglycale, anli-IgL lher-
ay, anlicholinergics, ciclesonide
and ossibly anli-inlerleukin 5 (IL-
5) lheraies have lhe olenlial lo
lreal differenl forms of aslhma.
Hovever, lhere remain many
challenges in idenlifying lhe many
varialions in aslhma manifeslalions.
Some challenges include lhe facl
lhal many alienls do nol resond
lo lrealmenl, many alienls have a
severe form of aslhma, and alienls
can gel vorse suddenly vhen slable
for years on slandard lheray.
In addilion, clinical fealures
differ from alienl lo alienl, co-
exisling allergic and non-allergic
diseases can cloud lhe diagnosis,
and lhe genelic basis for aslhma is
currenlly oor underslood, he said.
The severe form of non-allergic
aslhma is dehned as aslhma lhal
is oorly conlrolled chronically
and refraclory lo lrealmenl. Il in-
cludes only 5 lo 1O ercenl of er-
sons vilh aslhma bul accounls for
u lo 5O ercenl of aslhma-relaled
morbidily, morlalily and uliliza-
lion of heallhcare resources.
The American Thoracic Sociely
dehnes severe aslhma by lhe fol-
loving crileria: lrealmenl vilh
conlinuous or near conlinuous (~5O
ercenl of year) oral corlicosleroids,
high-dose inhaled corlicosleroids,
addilional daily lrealmenl vilh a
conlroller medicalion (eg, long-
acling bela-agonisl, lheohylline
or leukolriene anlagonisl), aslhma
symloms requiring shorl-acling
bela-agonisl use on a daily or near-
daily basis, ersislenl airvay ob-
slruclion, one or more urgenl care
visils for aslhma er year, lhree or
more oral sleroid 'bursls' er year,
roml delerioralion vilh a 25 er-
cenl reduclion in oral or inhaled
corlicosleroid dose, and near-falal
aslhma evenl in lhe asl. |j App|
Pnqsic| 2OO8,1O4:394-4O3j
Understanding of triggers crucia|
in treating non-a||ergic asthma

Any numbcr
nI rc!atIvc!y bcnIgn
trIggcrs can causc
a nnn-a!!crgIc
asthma cpIsndc
News
October 2011
nd
vn
me
an
on
mi-
ys
ors
nd
es-
,
de
L
hc
nls
29
4HS]PUKLYQP[2H\Y+OPSSVU
M
enoause in ilself is nol
associaled vilh a higher
risk of breasl cancer. As
vilh many olher cancers, lhe mosl
imorlanl risk faclor for breasl can-
cer is increased age, says a secialisl.
In lheory, uninlerruled ex-
osure of breasl lissue lo eslrogen
increases lhe risk of breasl cancer,
and lhis is seen in females vilh
early menarche (<12 years), lale
menoause (>55 years), lale hrsl
regnancy (>35 years) and have
never breaslfed before.
Lvidence suggesls lhal lhe lon-
ger a voman is exosed lo lhe fe-
male hormone, vhelher il's made
by lhe body or laken as a sule-
menl, lhe higher lhe chances of her
develoing breasl cancer, said Dr.
Ialricia A. Gomez, a consullanl
breasl surgeon.
Hovever, Gomez added, nol
having risk faclors does nol neces-
sarily mean one vill nol gel breasl
cancer as il is mullifaclorial and nol
all lhe faclors causing lhis disease
are knovn.
We are looking al relrosec-
live dala and surmising lhal lhose
vilh lhe knovn risk faclors have a
higher incidence of breasl cancer.
ul ve slill do nol knov all lhere
is lo knov aboul breasl cancer. If
you have lhe RCA gene, you are
al a higher risk, bul il slill does nol
mean you vill gel breasl cancer.
We do nol knov vhal svilches lhe
gene on, she lold Mc!icc| 1ri|unc.
Sludies shov lhal surgically
induced menoause decreases lhe
risk of breasl cancer by 6O ercenl
if done before lhe age of 65, and
lhal breasl cancer risk remains as
lov as one-lhird of lhe execled
risk 3O and more years laler. In
comarison, relalive risk of breasl
cancer increases vilh age, vhere
vomen vilh nalural menoause al
age 55 or older have lvice lhe risk
lhan lhose vho allain menoause
before lhe age of 45. |j Nci| Ccnccr
|nsi 1972,48(3):6O5-13j
Gomez also lold Mc!icc| 1ri|unc
lhal surgically inducing meno-
ause lovers lhe risk of breasl can-
cer as lhe absence of eslrogen ro-
lecls lhe breasl.
Asked if vomen vho have a
redisosilion lo breasl cancer
are advised lo surgically induce
menoause as a revenlalive
measure, Gomez said, Thal is a
ralher draslic sle lo lake, bul you
vill hnd lhal vomen vho nov
lesl osilive for lhe RCA I and II
genes are rohylaclically having
bilaleral masleclomies vilh re-
conslruclions and hyslereclomies
vilh bilaleral oohereclomies in
lhe US and Luroe.
The big difference is lhal
|lhese rocedures arej covered by
lheir insurance comanies, bul nol
by insurance comanies in Malay-
sia.
Worldvide, breasl cancer in-
cidence is highesl in develoed
regions, vhile morlalily is highesl
in underdeveloed regions. ||ni j
Ccnccr 2O1O,127(12):2893-917j The
raid rise of breasl cancer in devel-
oing counlries is oflen allribuled
lo lhe veslernizalion of lifeslyles
Menopause and the risk of breast cancer
|ncrccsc! cgc is cn impcricni risk jcr
|rccsi ccnccr.
such as childbearing raclices (lale
hrsl regnancies), breaslfeeding
raclices, exosure lo exogenous
eslrogen (hormone relacemenl
lheray or oral conlracelives)
and dielary habils (increased lrans
fals).
There is also a ronounced dif-
ference in breasl cancer incidence
in Asia comared vilh Auslralia
and Nev Zealand, vilh lhe rale in
Asia ranging from 15 lo 5O eole
er 1OO,OOO nalional oulalion,
and Auslralia and Nev Zealand
from 81.7 lo 84.7 er 1OO,OOO na-
lional oulalion.
Gomez said lhis difference is
due lo lhe facl lhal Auslralia and
Nev Zealand are mainly ou-
laled by Caucasians vho migral-
ed from Luroe, vhere lhere is a
higher incidence of breasl cancer,
and lhal lheir diels and lifeslyles
are similar lo lhose in Luroe.
3LVUHYK@HW
T
lymhocyles (T cells) can be
rogrammed lo hnd and de-
slroy cancer cells, shovs a recenl
sludy.
The sludy, ublished online in
lhe Ncu |ng|cn! jcurnc| cj Mc!i-
cinc, demonslraled lhal a alienl's
ovn T cells can be genelically mod-
ihed lo exress anlibodies on lheir
surface, giving lhem nev anligen
secihcily for chronic lymhocylic
leukemia (CLL). The nev anligen
recelors combine an anligen-rec-
ognilion domain vilh an inlracel-
lular domain of lhe CD3-zela chain
or IcaRI rolein inlo a single chime-
ric rolein, vhich has largel seci-
hcily for lhe -cell anligen CD19.
juuu.ncjm.crg/!ci/ju||/10.1056/
N|jMcc1103849?ucrq=jcciurc!_
ncmc-i=criic|c Accessed on 1O Au-
guslj
-cell CD19 is a useful largel
because ils exression is reslricled
only lo normal and malignanl -
cells or lheir recursors. There-
fore, re-inlroducing genelically
modihed T cells vould lrigger an
immune resonse againsl lhe of-
fending -cells, lhe sludy aulhors
said.
Three alienls vilh advanced
CLL vere lrealed using lhis lech-
nique. Clinical resonse lo lreal-
menl (recorded for one alienl)
vas observed afler 14 days, vilh
symloms of lov-grade fever and
chills associaled vilh grade 2 fa-
ligue. Tumor lysis syndrome vas
diagnosed on day 22 and by day
28, lhe absence of CLL vas ob-
served in lhe bone marrov.
Comlele remission vas re-
orled in one alienl and lhe
olher lvo alienls aeared lo
be resonding vell lo lrealmenl.
The osilive oulcome of lhis sludy
should sur more research inlo
lhe use of CD19-redirecled T cells
in CLL, lhe sludy concluded.
CLL is a disorder of morho-
logically malure, bul immunologi-
cally less malure, lymhocyles
vilh rogressive accumulalions
of lhese cells in blood, bone mar-
rov and lymhalic lissues. |Icncci
2OO8,371:1O17-29j
There is a large varialion in sur-
vival among individual alienls,
ranging from several monlhs lo
a normal life execlancy. |B|cc!
2OO5,1O5(1):2-3j
The ma|or causes of dealh
in CLL alienls are hemorrhage
and infeclion. |Ann |nicrn Mc!
1998,129(7):559-66j
T ce||s can be taught to
ki|| cancer ce||s

Thc pnsItIvc
nutcnmc nI thIs study
shnu!d spur mnrc rcscarch
Intn thc usc nI CD19-
rcdIrcctcd T cc!!s In CLL
1crgci spcciciiq jcr CD19 ui||
iriggcr cn immunc rcspcnsc.
News
October 2011
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30
(\KYL`>VUN
R
educing seven risk faclors
by 1O lo 25 ercenl could
revenl as many as 1.1 lo
3 million cases of Alzheimer's dis-
ease (AD) vorldvide, a recenl re-
viev suggesls.
Given lhe currenl absence of
disease-modifying lrealmenls, as
vell as increasing avareness lhal
symloms develo over many
years or even decades, lhere has
been groving inleresl in idenlihca-
lion of effeclive slralegies for re-
venlion of AD, exlained reviev
aulhors Dr. Deborah arnes and
Dr. Krisline Yaffe from lhe Univer-
sily of California, San Irancisco,
California, US. bservalional
sludies have idenlihed a vide
range of olenlially modihable risk
faclors for AD and demenlia.
Ior examle, u lo 5O ercenl
or 17.2 million of AD cases glob-
ally are olenlially allribulable lo
seven modihable risk faclors vhich
lhe aulhors idenlihed as lov educa-
lional allainmenl (cognilive inacliv-
ily), resenl smoking, hysical in-
aclivily, deression, midlife obesily,
midlife hyerlension and diabeles.
|1nc Icncci Ncurc| 2O11 19 }ul Lub
ahead of rinl DI:1O.1O161S1474-
4422(11)7OO72-2j
Analyses of dala from 146
counlries shov lhal lov educalion-
al allainmenl is a ma|or risk faclor
for AD, conlribuling lo lhe largesl
roorlion (19 ercenl, 6.5 million,
RR 1.59, 95/ CI 1.351.86) of cases
vorldvide.
As a risk faclor, il has an imor-
lanl global imlicalion said arnes.
The reviev hndings suggesled lhal
a 25 ercenl reduclion in lov edu-
calional allainmenl globally could
olenlially lover vorldvide AD
cases by aboul 1.4 million.
Smoking is anolher exlremely
common and imorlanl risk fac-
lor. Il resulls in lhe second highesl
number (14 ercenl, 4.7 million, RR
1.59, 95/ CI 1.152.2O) of AD cases
vorldvide. The aulhors eslimaled
lhal reducing smoking by 25 er-
cenl could in lurn reduce AD cases
globally by more lhan a million.
Whal really mallered vas
hov common lhe risk faclors vere
in lhe oulalion. In lhe USA,
aboul a lhird of lhe oulalion is
sedenlary, so a large number of
Alzheimer's cases are olenlially
allribulable lo hysical inaclivily,
arnes remarked.
Ihysical inaclivily conlribules
lo lhe lhird largesl roorlion (13
ercenl, 4.3 million, RR 1.82. 95/
CI 1.192.78) of AD cases vorld-
vide, bul accounls for lhe largesl
number (21 ercenl, 1.1 million, RR
1.82, 95/ CI 1.192.78) in lhe US. A
25 ercenl reduclion in hysical
inaclivily could revenl nearly 1
million cases globally and 232,OOO
cases in lhe US alone.
arnes and Yaffe used dala
from syslemalic revievs and mela-
analyses available on lhe Cochrane
dalabase of syslemalic revievs (all
years) and IubMed (2OO52O11) lo
eslimale lhe number of revenlable
AD cases lhal could be achieved by
reducing lhe burden of each of lhe
above-lisled risk faclors, vilh lhe
aim of idenlifying inlervenlions
lhal mighl be able lo delay lhe de-
velomenl of Alzheimer's disease.
|Tjhe mosl effeclive slralegies
for lovering AD revalence mighl
be ublic educalion camaigns
and smoking cessalion inilialives,
lhey suggesled. ecause hysical
inaclivily is associaled vilh mosl
of lhe olher AD risk faclors iden-
lihed...ublic heallh inilialives lo
increase hysical aclivily levels
lhroughoul life could olenlially
have a dramalic effecl on AD and
demenlia revalence over lime.
Addilionally, RCTs |random-
ized conlrolled lrialsj of mullimod-
al risk faclor reduclion slralegies lo
revenl AD are crucially needed,
lhe aulhors concluded.
G|oba| A|zheimer's burden can be reduced,
suggests review
Lnw cducatInna!
attaInmcnt Is a majnr
rIsk Iactnr Inr AD

News
October 2011
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31
,S]PYH4HUaHUV
D
isconlinualion of rolon
um inhibilors (IIIs)
lhe slandard of care for
gaslroesohageal reux disease
(GLRD) afler a shorl course of
lrealmenl for erosive esohagilis
does nol vorsen hearlburn sym-
loms or cause ersislenl hyergas-
lrinemia.
This vas a key hnding from a
relroseclive analysis of dala from
four hase III lrials of IIIs con-
ducled by Dr. David Melz, from
lhe Universily of Iennsylvania
School of Medicine, Ihiladelhia,
Iennsylvania, US and colleagues.
The resulls are reassuring in
lighl of earlier sludies shoving
lhal rebound acid hyersecrelion
(RAHS) occur afler III vilhdraval
and olher lrials demonslraling lhal
disconlinualion of shorl-lerm III
lheray could induce acid-relaled
symloms in heallhy volunleers.
Dala from our analysis conlra-
dicl |lhesej hndings, lhe aulhors
said.
In lhis nev sludy, 287 alienls
vilh Hc|icc|ccicr pq|cri-negalive
erosive esohagilis vho had re-
ceived 4 or 8 veeks lrealmenl vilh
dexlansorazole modihed release
(MR) or lansorazole and laler ran-
domized lo lacebo for 6-monlh
mainlenance lrials vere analyzed
for RAHS occurrence and for hearl-
burn severily. |Am j Gcsirccnicrc|
2O11, DI:1O.1O381a|g.2O11.22Oj
Resulls shoved no evidence
of RAHS uon disconlinualion of
III lheray. No change in mean
gaslrin values vere noled al main-
lenance monlhs 1 and 3 (1.O and
-1.O g1ml), indicaling lhal gaslrin
normalized vilhin 1 monlh of dis-
conlinuing IIIs and remained al.
Moreover, mean hearlburn se-
verily al mainlenance monlh 1 vas
<1 (1 mild on a 5-oinl scale) and
signihcanlly lover comared lo
baseline (P<O.OO1). In alienls vilh
monlh 2 dala, mean hearlburn
severily al monlhs 1 and 2 vas
signihcanlly lover lhan baseline
(P<O.OO1), indicaling an ongoing
symlom resonse 2 monlhs afler
III vilhdraval.
ur analysis shovs lhal dis-
conlinualion of 4 or 8 veeks of
III lheray did nol roduce any
evidence of relase of hearlburn
symlom severily lo levels vorse
lhan relrealmenl levels. Clearly,
lhere vas no indicalion lhal dis-
conlinualion of 4-or 8-veek course
of III lheray is causing III de-
endency, lhe aulhors concluded.
Hovever, lhe currenl hndings
do nol exclude lhe ossibilily of
9HKOH*OP[HSL

T
he associalion of severe sym-
loms of gaslroesohageal re-
ux disease (GLRD) vilh lhe de-
velomenl of esohageal cancers
may have been overeslimaled, ac-
cording lo a recenl sludy.
Conversely, alienls vho are
being lrealed for GLRD and vho
resenl vilh almosl no symloms
may be al higher risk for dyslasia
and esohageal adenocarcinomas.
In a cross-seclional sludy in-
volving 769 GLRD alienls vho
had a rimary screening endosco-
y belveen 2OO4 and 2OO7, 122 had
arrell's esohagus (L), vhich is
damage lo lhe esohageal cell lin-
ing due lo reealed acid exosure,
or adenocarcinomas. |Arcn Surg
2O11,146(7):851-858j
GLRD alienls vho received
lrealmenl vilh rolon um in-
hibilors (IIIs) vho reorled no
symloms vere 61.3 ercenl more
likely lo have an adenocarcinoma
comared lo alienls reorling se-
vere symloms. Ialienls reorling
alyical symloms such as cough,
excess mucus and hoarseness vere
81.5 ercenl more likely lo have
adenocarcinomas.
ecause lheir symloms are
absenl, insignihcanl, or alyical,
lhese alienls do nol seek medical
care or are nol selecled for endo-
scoic screening, and occull dis-
ease rogression ensues, said lhe
researchers, from lhe Universily
of Iillsburgh Medical Cenler in
Iennsylvania, US.
They added lhal lheir hnd-
ings highlighl holes in lhe currenl
rimary screening aradigm for
esohageal cancer, vhich counls
symlom severily as an imorlanl
indicalor of olenlial carcinogen-
esis.
Using lhe resence of long
slanding severe GLRD symloms
lo guide screening slralegies has
failed lo reduce lhe number of a-
lienls resenling vilh incurable
disease, said lhe researchers.
They noled lhal 95 ercenl of
alienls vilh esohageal adeno-
carcinomas had nol received rior
endoscoic screening nor had
lhey resenled vilh L. Advanced
esohageal cancer has a oor rog-
nosis.
In addilion lo masking lhe
lyical symloms of GLRD, acid
suressors aller acidic reux lo
non-acidic reux, vhich can slill
romole L. Aboul half of alienls
vilh L on IIIs resenl vilh veak
acid esohageal exosure, indical-
ing lhal alienls vilh fev or alyi-
cal symloms vould benehl from
L screening.
The researchers said lhey
could nol include some confound-
ers such as obesily or duralion of
GLRD symloms in lheir analysis
due lo lhe nalure of lheir dala, and
lhal inclusion may have revealed
a differenl relalionshi belveen
GLRD symloms and esohageal
adenocarcinoma.
Slill, lhe olenlial ilfalls of
long-lerm III use in GLRD a-
lienls are coming lo lighl.
We are learning lhal lhe
chronic and long-lerm use of IIIs
may nol be enlirely vilhoul con-
sequences and may lead lo more
insidious roblems such as cal-
cium malabsorlion or cause one
lo be asymlomalic in lhe face of
conlinued esohageal in|ury from
GLRD, said rincial invesliga-
lor Dr. lair }obe, rofessor and di-
reclor of esohageal research and
esohageal diagnoslics and lhera-
eulic endoscoy in lhe Dearl-
menl of Cardiolhoracic Surgery al
lhe Universily of Iillsburgh School
of Medicine.
Heartburn not |ike|y to worsen after PPl withdrawa|
5evere GERD
symptoms not |inked
to esophagea| cancer
RAHS folloving disconlinualion
of long-lerm III lheray.
The aulhors said lhey see no
reason for clinicians lo change lheir
rescribing habils ending more
comelling and consislenl dala on
IIIs. We recommend lhal hysi-
cians conlinue lo follov lhe 2OO8
American Gaslroenlerological As-
socialion (AGA) guidelines, vhich
slale lhal emirical lheray vilh
IIIs is considered aroriale lo
iniliale lheray in alienls vilh
uncomlicaled hearlburn.
|cr|icr siu!ics nc! suggcsic! rc|cun!
cci! nqpcrsccrciicn
October 2011
GERD
Our ana!ysIs shnws
that dIscnntInuatInn
nI 4 nr 8 wccks nI PPI
thcrapy dId nnt prnducc
any cvIdcncc nI rc!apsc
nI hcartburn

FIndIngs hIgh!Ight hn!cs

In thc currcnt prImary
scrccnIng paradIgm Inr
csnphagca! canccr

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32
Humor
October 2011
For the peace of mind of our
patients, could you dispense
with your You might not be
seeing me again speech!
Youre next Mr. Pinkerton!
I got your tests back. Your kidneys, liver and heart are all ne.
Its your shirt that Im worried about!
Which one do you think the fetus
would be most happy hearing
Mozarts Don Giovanni or Snoop
Dogs Malice n Wonderland?
Let me nd out if this side effect
has ever been reported!
I hate to tell you this ... but we
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No question its hereditary.
My uncle Fred treated your Uncle
Bob for exactly the same illness!
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33
C
onslialion is a common chronic
roblem lhal involves lhe reduclion
in frequency and volume of bovel
movemenls, in addilion lo a drier consislen-
cy and slraining al defecalion.
Normal bovel movemenl frequency is
belveen lhree limes er day and lhree limes
er veek. A ersislence of less lhan lhree
movemenls er veek lasling belveen 3 and
6 monlhs shifls lhe diagnosis lo chronic con-
slialion.
DIct nItcn dIctatcs cnnstIpatInn
Conslialion is frequenlly relaled lo di-
elary habils. verall inadequale inlake, ex-
cessive hber consumlion, lack of exercise,
deferring lhe urge lo ass molion, laxalive
abuse and environmenlal changes such as
hosilalizalion or lravel may resull in con-
slialion.
Slruclural and funclional disorders can
lead lo conslialion. bslruclion of lhe anal
shinclers or lhe colon (olys, lumors, di-
verlicular disease vilh slriclure) can block
slool assage. Cerlain visceral neuroalhies
or myoalhies, including Hirschrung's dis-
ease or Chagas' disease can cause conslia-
lion, as can irrilable bovel syndrome and
olher idioalhic disorders.
Cerlain medicalions are imorlanl con-
lribuling faclors lo chronic conslialion.
Cough medicine, codeine, anlideressanls,
iron sulemenls, anlicholinergics and
blood ressure medicalions can resull in dif-
hcully assing molion.
Conslialion may also be lhe resull of
some sychosocial disorders such as deres-
sion, anxiely or anorexia nervosa.
Hormonal and melabolic imbalances
such as hyolhyroidism can also resull in
conslialion.
TcstIng Inr cnnstIpatInn
asic examinalions vhich GIs can do in-
clude checking for bloaling, dislension and
imacled slool, and erforming fecal occull
blood lesls. lood lesls for cerlain biomark-
ers (HbA1c, free T4 and TSH) can hel de-
lermine if conslialion is disease-relaled.
Colonoscoy, barium enemas and CT colo-
nograhy exams hel vilh visual diagnosis.
A delailed alienl hislory and a clear un-
derslanding of lheir dielary habils can hel
inoinl causes of conslialion, bul alienls
may misreresenl or miss-recall lheir recenl
food inlake, vhich lhe GI should be avare
of. A food diary can hel vilh recall.
There are no clinical guidelines lhal se-
cihcally oulline besl raclices for diagnosing
chronic conslialion as cases vary greally be-
lveen alienls.
Dielary modihcalion is lhe hrsl sle for
lrealing olhervise heallhy alienls vilh
chronic conslialion. Lnsuring lhe correcl
balance of soluble and insoluble hbers and
valer over lhe course of lhe day can hel a
alienl regularize. Soluble hbers can include
cellulose, eclin, slarches and gums vhile
insoluble hbers include grain husks, oals,
cereals and bran. Soluble hbers are more ef-
feclive in slool soflening.
Irobiolics live bacleria found nor-
mally in lhe large inlesline and slool are
imorlanl lo kee lhe colon environmenl
heallhy, and lhese can be found in yogurls
or from sulemenls. The bacleria hel lo
increase bulk and kee uid in lhe slool lo
kee il sofl.
More dielary hber is nol alvays lhe an-
sver, hovever, because il may cake slool.
Ialienls should also be advised againsl
being sedenlary and lo increase lheir daily
hysical aclivily.
McdIca! IntcrvcntInns
If modifying diel has no effecl, suosi-
lories lo loosen slool and laxalives lo ease
bovel movemenl may be indicaled. Laxa-
lives, if necessary, should be adminislered
vilh ascending slrenglh lo revenl alienls
from adaling lo medicalion. A mild calhar-
lic or mechanical cleanser is a referred slarl-
ing olion.
Slimulanl laxalives, like anlhracene,
caslor oil, hyosine and dihenylmelhane
calharlics, in arlicular may be habil-form-
ing. Mechanical cleansers, including saline
laxalives, olyelhylene glycol, bulk form-
ing agenls, mineral oil and oloxalkol, can
be genller, bul should be used |udiciously as
vell.
In some funclional cases, alienls may
have normal slool, bul exerience difhcully
in assing molion due lo an inabilily lo re-
lax lhe anal shincler comlex. Shincler
sasms may occur and alienls enler a cycle
of feeling lhe need lo ass molion and being
unable lo do so, so lhey may give u lrying
leading lo chronic conslialion.
iofeedback, or behavioral modihcalion
lheray, can hel re-lrain such alienls lo re-
lax or aroach lheir roblem in a differenl
vay in order lo roerly ass molion. This
may include lechniques like brealhing exer-
cises and lo adequalely slrain vilhoul ara-
doxical shincleric conlraclion.
Surgery may be indicaled for alienls
vilh analomical hysical obslruclions like
megacolon, volvulus and lumors, and lheir
oulcomes are usually good.
Ialienls on medicalions, esecially long-
lerm medicalions such as lhose for high
blood ressure, need lo be managed careful-
ly as lhey may nol be able lo disconlinue lhe
conslialion-causing drug. Trealmenl may
slill begin vilh dielary modihcalion bul su-
osilories and laxalives may also be used.
Ialienls should be referred lo a secialisl
for furlher lesls and lrealmenl if lheir condi-
lion ersisls beyond 3-6 monlhs bul can be
managed in lhe communily afler inilial eval-
ualion vilh colonic imaging and suilable
biochemical lesls lo exclude hyolhyroidism
and diabeles mellilus. Chronic deression is
also relaled lo conslialion.
Ialienl follov u includes educaling
lhem as lo lhe cause of lheir chronic con-
slialion and hov dielary, lifeslyle, drug or
behavioral modihcalions need lo be main-
lained lo encourage regularily. Laxalives
may be used lo moderale lhe severily.
Cnnc!usInn
Chronic conslialion is a fairly common
condilion lhal resulls in an inabilily lo ass
molion. Diel and hysical aclivily are fre-
quenl causes bul cerlain medicalions and
sychosocial condilions may also be lead lo
conslialion. Dielary and lifeslyle modihca-
lion is lhe hrsl sle for almosl every case of
chronic conslialion, lhough suosilories
and laxalives may be required in con|unclion
in cases vhere non-medical modihcalions
fail lo vork. iofeedback lechniques may
also be useful for alienls vho do nol have
oor slool bul have difhcully having bovel
movemenls.
eyond inilial secialisl assessmenl, GIs
are vell osilioned lo conlinue caring for a-
lienls vilh chronic conslialion in lhe com-
munily.
Managing chronic constipation in primary care
Dr. Tang Choong Leong
Head and Senior Consultant
Department of Colorectal Surgery
Singapore General Hospital
On|ine Resources:
AmcrIcan SncIcty nI Cn!nn and Rccta!
Surgcnns
vvv.fascrs.org
AmcrIcan DIctctIc AssncIatInn
vvv.ealrighl.org
AmcrIcan Cn!!cgc nI Gastrncntcrn!ngy
vvv.acg.gi.org
Cnrcnic ccnsiipciicn is c jcir|q ccmmcn ccn!iiicn rcsu|iing in cn inc|i|iiq ic pcss mciicn.
DIctary and !IIcsty!c mndIcatInn Is thc rst stcp
Inr a!mnst cvcry casc nI chrnnIc cnnstIpatInn, thnugh
suppnsItnrIcs and !axatIvcs may bc rcquIrcd

BasIc cxamInatInns whIch GPs can dn Inc!udc

chcckIng Inr b!natIng, dIstcnsInn and Impactcd stnn!,
and pcrInrmIng Icca! nccu!t b!nnd tcsts

I n Pr act i ce
October 2011
34
Cal endar
October 2011
October
Great Wall International Congress
of Cardiology
13/10/2011 to 16/10/2011
Location: Beijing, China
Info: Great Wall International Congress
of Cardiology Organizing Committee
Tel: (86) 1088324876
Email: secretariat@gw-icc.org
Website: www.gw-icc.org
8th MOS Annual Scientic Meeting
14/10/2011 to 16/10/2011
Location: Subang Jaya, Malaysia
Info: Malaysian Osteoporosis Society
Tel: (603) 7718 1720
Email: hui.cheng.ng@merck.com
Website: www.osteoporosis.my
2011 Scientic Assembly of the
American College of Emergency
Physicians
15/10/2011 to 18/10/2011
Location: San Francisco, California,
US
Info: American College of Emergency
Physicians
Email: meetingsregistrar@acep.org
Website: www.acep.org
67th Annual Meeting of the
American Society for Reproductive
Medicine
15/10/2011 to 19/10/2011
Location: Orlando, Florida, US
Info: American Society for Reproduc-
tive Medicine
Email: asrm@asrm.org
Website: www.asrm.org
97th Annual Meeting of the
American College of Surgeons
23/10/2011 to 27/10/2011
Location: San Francisco, California,
US
Info: American College of Surgeons
Email: postmaster@facs.org
Website: www.facs.org
12th Congress of the International
Society of Hematology, Asia Pacic
Division & HAA 2011
30/10/2011 to 2/11/2011
Location: Sydney, Australia
Info: International Society of Hematol-
ogy Asia Pacic Division
Email: HAA@fcconventions.com.au
Website: www.ishapd.org
November
8th Asian Pacic Congress of
Hypertension
1/11/2011 to 1/11/2011
Location: Taipei, Taiwan
Info: Asian Pacic Society of Hyperten-
sion
Email: secretary@apsh.org
Website: www.apsh.org
2011 Annual Meeting of the
American College of Allergy,
Asthma and Immunology
3/11/2011 to 8/11/2011
Location: Boston, Massachusetts, US
Info: American College of Allergy,
Asthma and Immunology (ACAAI)
Email: meetings@acaai.org
Website: www.acaai.org
16th Congress of the Asia Pacic
Society of Respirology
3/11/2011 to 6/11/2011
Location: Shanghai, China
Info: UBM Medica, Shanghai, China
Tel: (86) 21 6157 3888 ext.
3861/3862
Email: secretariat@apsr2011.org
Website: www.apsr2011.org
10th World Congress of Perinatal
Medicine
8/11/2011 to 11/11/2011
Location: Punta del Este, Uruguay
Info: World Association of Perinatal
Medicine
Email: 10wcpm@personas.com.uy
Website: www.10wcpm.info
21st Asia Pacic Cancer Conference
10/11/2011 to 12/11/2011
Location: Kuala Lumpur, Malaysia
Info: AOS Conventions
Email: apcc2011@aosconventions.com
Website: www.apcc2011.com
22nd Regional Congress of the
International Society of Blood
Transfusion, Asia
16/11/2011 to 19/11/2011
Location: Taipei, Taiwan
Info: Eurocongress International
Email: isbt.taipei@eurocongress.com
Website: www.isbt-web.org
72nd Annual Assembly of the
American Academy of Physical
Medicine and Rehabilitation
17/11/2011 to 20/11/2011
Location: Orlando, Florida, US
Info: American Academy of Physical
Medicine and Rehabilitation
Email: info@aapmr.org
Website: www.aapmr.org
Upcoming
2011 American Epilepsy Society
Annual Meeting
2/12/2011 to 6/12/2011
Location: Baltimore, Maryland, US
Info: American Epilepsy Society
Email: csluboski@aesnet.org
Website: www.aesnet.org
22nd World Allergy Congress
4/12/2011 to 8/12/2011
Location: Cancun, Mexico
Info: World Allergy Organization
Tel: (1) 414 276 1791
Email: WAC2011@worldallergy.org
Website: www.worldallergy.org/
wac2011
6th Asia Pacic Congress of Heart
Failure
3/2/2012 to 5/2/2012
Location: Chiang Mai, Thailand
Info: Lawson-Marsh Events Co., Ltd.
Tel: + 66 (0) 2940-2483
Fax: + 66 (0) 2940-2484
Email: apchf2012@lawson-marsh.
com
Website: www.apchf2012.com
Medical progress

through
CME in print
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35
*DPP-4 = dipeptidyl peptidase-4.
**JANUVIA and JANUMET are indicated for triple therapy in type 2 diabetes mellitus.
For patients with type-2 diabetes mellitus:
JANUMET is indicated as initial therapy in adult patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise do not
provide adequate glycemic control. JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with
type 2 diabetes mellitus who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the
combination of sitagliptin and metformin. JANUMET is also indicated in combination with a sulfonylurea (i.e., triple combination therapy) as an
adjunct to diet and exercise in adult patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: metformin,
sitagliptin, or a sulfonylurea. JANUMET is indicated as add-on to insulin (i.e., triple combination therapy) as an adjunct to diet and exercise to
improve glycemic control in patients when insulin and metformin alone do not provide adequate glycemic control.
JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus as initial therapy,
alone or in combination with metformin. JANUVIA is indicated in combination with metformin, sulfonylurea, PPAR agonist, metformin and a
sulfonylurea when the current regimen, with diet and exercise does not provide adequate glycemic control. JANUVIA is also indicated as add-on
to insulin (with or without metformin) when diet and exercise plus stable dose of insulin do not provide adequate glycemic control.