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www.medicaltribune.com
May 2012
Dramatic blood sugar control withgastric surgery
FORUM
Biobanks: Research dream or
ethical nightmare?
CONFERENCE
Cardiac pacing reduces
syncope recurrence
IN PRACTICE
Managing acute os media:
Strategies for GPs
AFTER HOURS
The science of food avors
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2 May 2012
Radha Chitale
Gastric surgery controlled blood sugarbeer than intensive medical therapyamong obese type 2 diabetics, according to
the STAMPEDE trial, the results of which
were presented at the 61st Annual Scientic
Sessions of the American College of Cardiol-
ogy meeting in Chicago, Illinois, US.
Patients who underwent Roux-en-Y gas-
tric bypass surgery or sleeve gastrectomy
achieved HbA1c control below 6 percent
within a year in 42 percent (P=0.002) and
37 percent of cases (P=0.008), respectively,
compared with 12 percent who received in-
tensive medical therapy alone. [N Engl J Med
2012 Mar 26. Epub ahead of print]
Despite improvements in pharmacother-
apy, fewer than 50 percent of patients with
moderate-to-severe type 2 diabetes actually
achieve and maintain therapeutic thresholds,
particularly for glycemic control, said re-
searchers from the Cleveland Clinic in Ohio,
US, Veterans Aairs Boston Healthcare Sys-
tem and Brigham and Womens Hospital inBoston, Massachuses, US.
Observational studies have suggested
that bariatric or metabolic surgery can rap-
idly improve glycemic control...
The trial randomized 150 obese patients
(mean age 49 years, mean body mass index
36 kg/m2, mean HbA1c 9.2 percent) with un-
controlled type 2 diabetes to receive inten-sive medical therapy alone, medical therapy
plus Roux-en-Y gastric bypass surgery ormedical therapy plus sleeve gastrectomy.
Intense medical therapy followed the
guidelines of the American Diabetes Asso-
ciation and included lifestyle counselling,
weight management, and drug therapy.
Patients randomized to surgery experi-
enced signicantly more weight loss com-
pared with those receiving medical therapyaer 12 months (-29.5 kg gastric bypass, -25.1
kg sleeve gastrectomy, -5.4 kg medical ther-
apy, P
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3 May 2012
7.5 percent among patients receiving medi-
cal therapy.
Patients who underwent surgery also sig-
nicantly reduced or halted use of glucosecontrol and cardiovascular medications.
Reductions in the use of diabetes medica-
tions occurred before achievement of maxi-
mal weight loss, which supports the concept
that the mechanisms of improvement in dia-
betes involve physiologic eects in addition
to weight loss... the researchers said.
No deaths or life threatening complicationsoccurred although four patients required a
second surgery for complications.
In an accompanying comment, Dr. Paul
Zimmet, Baker IDI Heart and Diabetes Insti-
tute, Melbourne, VIC, Australia, and Dr. K.
George M. M. Alberti, Kings College Hospi-
tal, London, England, said surgery would not
be the universal panacea for obese patients
with type 2 diabetes and pointed out that thestudy duration was only 1 year and that sur-
gery has inherent hazards. [N Engl J Med 2012
Mar 26. Epub ahead of print]
There is also the problem of remission
versus cure, they said. Type 2 diabetes is
oen progressive, and worsening of glycemic
control over time is likely in many patients.
However, some years of improved glycemiamay well result in less microvascular disease.
Both the researchers and commenters
called for further studies on the long-term
clinical eects of gastric surgery.
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4 May 2012
New guidelines urge tailored approach inhyperglycemia
Rajesh Kumar
The European Association for the Studyof Diabetes (EASD) and the AmericanDiabetes Association (ADA) have issued joint
guidelines, calling for a more patient-centred
approach in the treatment of hyperglycaemia
in people with type 2 diabetes.
The wide range of pharmacological choic-
es, conicting data about some of those choic-
es, and dierences in how patients respond to
medications makes it dicult to prescribe a
single treatment that will work for everyone.
The document discusses in detail the avail-
able evidence on a growing number of phar-
macological agents including metformin,
sulfonylureas, thiazolidinediones, DPP-4 in-
hibitors, GLP-1 receptor agonists, and dier-
ent types of insulin, and calls for all patients
with diabetes to receive personalized diabe-
tes education, focused on dietary intervention
and the importance of physical activity.
The guidelines also recommend that com-
prehensive cardiovascular risk reduction be a
major focus of therapy.
Professor David Mahews, chairman of
the EASD panel for overseeing guidelines
and statements, said while pharmacological
options are geing wider, the evidence base
has become smaller.
The consensus that we have come to [with
the ADA] is that we need individualization of
the [HbA1c] targets and it depends on the pa-
tients comorbidities and environments as to
what the target should be, said Mahews,
who works at the UK National Institute for
Health Research (NIHR), Oxford Biomedical
Research Centre, Oxford, UK.
The new guidelines take a more holistic
approach, focusing on treating the patient as
an individual, added EASD president Profes-
sor Andrew Boulton. [The] approach will
likely improve not only patient care, but also
quality of life.
The consensus that
we have come to
[with the ADA] is that
we need individualization of
the [HbA1c] targets
Therefore, physicians should consider in-
dividual patients needs, preferences andtolerances and consider that type 2 diabetes
patients dier substantially in terms of age,
disease progression and co-morbidities, the
two organizations said in a position state-
ment [Diabetologia 2012; DOI:10.1007/s00125-
012-2534-0, Diabetes Care 2012; Apr 19;
DOI:10.2337/dc12-0413].
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5 May 2012 Forum
Biobanks: Research dream orethical nightmare?
Professor Alastair V. Campbell, Director of the Centre for Biomedical Ethics at the National
University of Singapore, discussed the research potential of large-scale human health data-
bases during the Asia-Pacic Research Ethics Conference, held recently in Singapore.
Biobanks, large epidemiological cohorts,including past and present populations,that are associated with extensive samples of
DNA and other biological materials, linked
to health data, oer a rich source of informa-
tion for public health research. Data capture
health episodes aecting participants as they
occur and are oen followed up for decades.
However, the possibility of information abuse
or use for commercial gain is high. Creating
and maintaining biobanks raises a number of
major ethical questions that should be dealt
with as we strive to dene and defend the bio-
commons.
Opportunities for research
Biobanks warrant unusual consideration.
The data they contain oer a broad range of
possible research opportunities, mined from
a broad range of future health information
that will be captured. This is large-scale data,with many participants, making it somewhat
impersonal. In addition, a range of research-
ers will have access to the data for a very long
time.
The major features that make a biobank
enterprise dierent from a piece of research
are the need for general consent, appropriate
stewardship, and justied trust.
Therefore, special measures are required
for biobanks, rather than holding them to the
same standards of research protocol as other
data sets.
The UK Biobank is the worlds largest re-
source of genetic health and lifestyle data. It
includes over 500,000 participants aged 40-
69 and has the unique advantage of gaining
data from the comprehensive British National
Health Service.
This biobank took about 10 years of leadtime in order to clarify the governance and
ethical framework, in addition to public con-
sultations. People would get a leer inviting
them for an assessment at a clinic. A major
part of the visit was spent explaining what
they were giving consent to.
Participants in the UK Biobank consented
to access to medical records for the remainder
of their lives and aer their death, without
feedback on the results of their testing, other
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6 May 2012 Forum
than minor initial tests for basic things like
blood pressure levels.
Consent for use of participant data is re-
scindable but not conditional. That is, you
cannot specify what type of research you arewilling to allow your tissues to be used for.
The big brother scenario
The nightmare scenario would be that big
brother is watching. How can we be sure
such databases wont be used in ways other
than what the participant signed up for? If, for
example, stored genetic information could beaccessed by court order in a society where au-
thorities increasingly want access to citizens?
In addition, if the commercial dominates, the
whole purpose of the collection is in danger.
This is where ethics in governance comes
in. If the ethics governing body believes the
participants trust was abused, they say so,
acting as proxy for the people involved.
The governance of the UK Biobank is in-dependent, and they alone guard the ethics
and governance framework. They advise on
revisions, monitor the UK Biobank and re-
port their ndings publicly and provide gen-
eral advice.
This kind of data consolidation lends itself
to growing into virtual biobanks. Virtual bio-
banks are gaining popularity as researchers
push to share and use population informa-
tion across regions.The issue of access is important in the face
of pressure to link data sets internationally
but it is complicated because there is no con-
sistency in governance across international
biobanks.
Ethicists could discuss whether it is right
to trust international entities with biobank
data without international consistency.
Security measures are important to have
in place to prevent inappropriate access.
Stewards must address who has access to the
biobank data, to what extent access to other
records is controlled and how easy it is to
hack into the resource.
Safeguards to prevent abuse
One solution could be for a virtual bio-
banks to link registries with safeguards to
prevent identication. A person would be as-
signed a serial number and the serial number
is linked to the health data as a way to store
data without compromising the safety of the
subject. The link would be stored with an in-
dependent trusted third party and without
their cooperation, no one can link the healthinformation back to the original subject.
Whatever the problems with broad consent,
presumed consent is not sucient. Biobanks
are more than just a collection of tissue or data.
Researchers have to see these as public prop-
erty for the common good, uninuenced by
commercial or nationalist interests. The pros-
pect for large-scale data sharing for health
not prot could lead to greater informationand more justice in healthcare.
Creating and maintaining
biobanks raises a number of
major ethical questions that should
be dealt with as we strive to dene
and defend the biocommons
Biobanks can be built from the ground
up, as the UK Biobank was, but they can
also be created by linking existing collectionsof tissue and registry information.
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7 May 2012 Hong Kong Focus
Noninvasive prenatal test forDowns syndromeChristina Lau
Noninvasive prenatal diagnosis of Downssyndrome is now available as a clinicalservice in Hong Kong, providing a safer and
less stressful alternative for pregnant women.
The test, called safeT21 (sensitive analysis
of fetal DNA for T21 screening), is the result
of 15 years of research at the Chinese Uni-versity of Hong Kong (CUHK). Using high-
throughput DNA sequencing technology, the
test analyzes millions of DNA fragments in
maternal blood to determine if there is an el-
evation in chromosome 21 DNA molecules,
which suggests the presence of a fetus with
Downs syndrome, said Professor Dennis Lo
of the Department of Chemical Pathology.
The test is based on Los discovery in 1997that cell-free fetal DNA is present in maternal
plasma as short fragments among primarily
maternally derived DNA fragments. [Lancet
1997;350:485-487] Subsequently, the research
team found that the entire fetal genome is in-
deed present in maternal plasma. [Sci Transl
Med 2010;2:61ra91]
The ndings led to the development of
a groundbreaking sequencing technologythat enabled the researchers to construct a
genome-wide genetic map and determine the
mutational status of the fetus from the mater-
nal plasma DNA sequences and from infor-
mation about the paternal genotype and ma-
ternal haplotype.
The safeT21 test accurately detects 99.1
percent of fetuses aected by Downs syn-
drome. The false positive rate is 0.1 percent,
said Lo. The diagnostic accuracy has been
validated by us in a large cohort of samples,
and in a large number of clinical studies con-
ducted by other groups around the world.The test is currently available at prenatal
diagnostic units at CUHK, Hong Kong San-
atorium & Hospital, Union Hospital, Hong
Kong Baptist Hospital, and a number of
obstetric group practices.
Downs syndrome is conventionally diag-
nosed by analyzing genetic material obtained
directly from the fetus through invasive pro-
cedures, such as amniocentesis and chorion-ic villus sampling. However, these invasive
procedures are associated with a miscarriage
rate of 0.5 to 1 percent, explained Lo. Its
envisioned that the noninvasive technology
will be increasingly used by centers around
the world, leading to substantial reductions
in the number of invasive prenatal diagnostic
procedures required.
Further information on the safeT21 test
may be obtained by calling 2632 1192.
Prof. Lo introducing the test
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8 May 2012 Hong Kong Focus
Early, intensive disease control advocatedin RANaomi Rodrig
Frequent monitoring and therapy ad-justment in the early stage of rheuma-toid arthritis (RA) can reduce disease activ-
ity and improve patients physical function,
according to a pilot study at the Queen
Elizabeth Hospital. [Hong Kong Med J 2012;
18:108-114]Twenty patients with RA onset of
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9 May 2012 Hong Kong Focus
Molecular studies highlight hazards ofTCM use
Two recently published molecular studiesreveal that ingredients used in traditionalChinese medicine (TCM) preparations are of-
ten dangerous as well as illegal.
Data reported in PNAS last month showed
that exposure to aristolochic acid a common
component of various TCM products is a
primary cause of urothelial carcinoma of the
upper urinary tract (UUC). The researchers,
led by Dr. Arthur Grollman of Stony Brook
University, New York, USA, conducted a
molecular epidemiologic study of UUC in
Taiwan, where its incidence is the highest
reported anywhere in the world and where
Aristolochia herbal remedies have been used
extensively for many years. [Doi: 10.1073/
pnas.1119920109]
Following metabolic activation, aristoloch-
ic acid reacts with DNA to form aristolactam
(AL)-DNA adducts. These lesions concentrate
in the renal cortex, where they serve as a sen-
sitive and specic biomarker of exposure, and
are found also in the urothelium, where they
give rise to a unique mutational signature in
the TP53 tumor-suppressor gene.
Sequencing of tumor samples (151 UUCand 25 renal cell carcinomas) revealed that
among patients with the characteristic TP53
mutations, 83 percent also showed the unique
molecular signature of exposure to aristolo-
chic acid.
We conclude that exposure to aristolochic
acid contributes signicantly to the incidence
of UUC in Taiwan, a nding with signicant
implications for global public health, the au-thors wrote.
In the second study, investigators at Mur-
doch University, Perth, Australia used high-
throughput DNA sequencing technology to
analyze 15 TCM samples (powders, tablets,
capsules, akes, and herbal teas) seized by
Australian customs ocials. [Doi: 10.1371/
journal.pgen.1002657]
In total, we found 68 dierent plant fami-
lies in the medicines they are complex mix-
tures of species, reported lead investiga-
tor, Dr. Michael Bunce. Some of the TCMs
contained plants of the genus Ephedra and
Asarum. These plants contain chemicals that
can be toxic if the wrong dosage is taken, but
none of them actually listed concentrations
on the packaging. We also found traces from
trade-restricted animals that are classied as
vulnerable, endangered, or critically endan-
gered, including the Asiatic black bear and
Saiga antelope.
Another concern is the mislabelling of
TCMs, meaning that consumers are unaware
of the presence of some ingredients, includ-
ing animal DNA and potential allergens such
as soy or nuts. Incorrect labelling also makes
it dicult to enforce legislation and to pros-ecute cases of illegal trade.
It is hoped that this new approach will
help to genetically audit medicinal prod-
ucts and bring about a new level of regula-
tion to the area of complementary and alter-
native medicine, said Bunce. TCMs have
a long cultural history, but today consum-
ers need to be aware of the legal and health
safety issues before adopting them as atreatment option. -NR
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10 May 2012 Hong Kong Focus
Beware of biosimilars, professionals andauthorities toldChristina Lau
Healthcare professionals and authoritiesin Hong Kong need to be watchful of bi-osimilars as more are anticipated to enter the
market following patent expiry of a few bio-
logics in the near future.
Many new-generation biologics will be o-
patent soon, including at least one monoclonal
antibody for cancer [trastuzumab] and one bio-logic for rheumatoid arthritis [etanercept] in the
next 2 to 3 years, said Associate Professor Viv-
ian Lee of the School of Pharmacy, Chinese Uni-
versity of Hong Kong. As partial disclosure of
the manufacturing procedure is required aer
patent expiry, emergence of biosimilars is an-
ticipated in the near future so that patients can
benet from lower-priced replicated drugs.
However, Lee cautioned that due to the com-plexity of biologics production, and the key dif-
ferences in how biosimilars and biologics are
manufactured, biosimilars are only similar
rather than identical to the original biologics.
Biologics are produced with top-notch bio-
technology and involve more than 5,000 critical
steps. Even slight deviations can lead to far-
reaching consequences on drug ecacy and
safety, she explained.For example, 175 cases of pure red cell apla-
sia [PRCA] were reported in France, Canada, UK
and Spain in 1998-2004 with the use of epoetinum
alfa, a biologic for anemia in patients with kidney
failure. In aected patients, epoetinum alfa led to
cessation rather than boosting of red blood cell
production. [N Engl J Med 2004;351:1403-1408]
Scientists suspected that the PRCA was due
to slight deviations in the manufacturing process
of epoetinum alfa, said Lee. In Hong Kong, no
PRCA was reported, but the drug was complete-
ly recalled later to ensure patient safety.
Production of biologics starts with the cre-
ation of a unique cell line, which is exclusively
owned by the original innovator. Manufactur-
ers of biosimilars can only use a similar cell
line, she explained. The complex molecules
or gene extraction involved in the production ofbiologics also make replication very dicult.
Furthermore, as the end products are highly
susceptible to changes in pressure, tempera-
ture, oxygen level, storage and transportation,
drug ecacy and safety maybe aected if any
of these factors are not well controlled.
In the past, phase III clinical data and post-
registration pharmacovigilance were not re-
quired of biosimilars. Close monitoring in theseareas is needed to ensure the ecacy and safety
of biosimilars in the long term, stressed Lee.
International health authorities have indeed
realized the importance and urgency of impos-
ing strict monitoring on biosimilars. The WHO,
US FDA and European Medicines Agency
(EMA) have either released or started formulat-
ing guidelines and regulations on the research
and quality data, safety, purity, potency, andpharmacovigilance required of biosimilars.
Compared with chemical drugs that have
been used for years, the ecacy and safety of bi-
osimilars are relatively less familiar to the phar-
maceutical industry and the Hong Kong gov-
ernment, pointed out Lee. Local authorities
should catch up with the global trend and start
formulating guidelines on the approval of bi-
osimilars in Hong Kong. Phase III clinical study
and pharmacovigilance should be required.
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11 May 2012 Hong Kong Focus
Enhancing stroke services: A priorityChristina Lau
Implementation of territory-wide 24-hourstroke thrombolysis service should be apriority for the local health authority as the
intervention is safe and associated with beer
outcomes, a new study suggests.
In the historical cohort study, researchers
from the Chinese University of Hong Kong
and Prince of Wales Hospital compared the
outcome of acute ischemic stroke patients
treated with IV tissue plasminogen activator
between October 2008 and May 2011 (n=48)
with those admied during the same period
who were thrombolysis-eligible, but treated
conservatively due to unavailability of throm-
bolysis service aer-hours (n=63). [Hong Kong
Med J2012;18:92-98]
At 3 months, 52 percent of patients in the
thrombolysis group achieved functional inde-
pendence vs 24 percent in the non-thrombolysis
group (p=0.003). There was no signicant in-
crease in mortality (15 vs 13 percent) or symp-
tomatic intracranial hemorrhage (4 vs 2 percent).
Thrombolysis treatment was also associated
with shorter hospital stay (mean, 25 days vs 35
days in the non-thrombolysis group; p=0.034).Twenty-nine percent of patients in the throm-
bolysis group were discharged home directly
vs 6 percent in the non-thrombolysis group
(p
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12 May 2012 Hong Kong Focus
Long influenza season takes heavy tollNaomi Rodrig
The 2011/2012 influenza season in HongKong, which continued with high ac-tivity well into April, was characterized
by changing infection trends and a high
mortality rate, according to surveillance
data from the Center for Health Protection
(CHP).
By April this year, the number of inuenza
detections at the Public Health Laboratory
Center remained high, at around 500 cases
per week.
While there was a decrease in the number
of inuenza B detections, the number of in-
uenza A (H3N2) detections showed a ris-
ing trend. For example, the weekly number
of inuenza B detections decreased from 339
to 173 between mid-March and early April,
whereas the weekly number of inuenza A
(H3N2) detections increased from 117 to 316
for the same period.
In early April, the main circulating inu-enza viruses were the inuenza A (H3N2) vi-
rus (64.4 percent), followed by the inuenza
B (35.2 percent) and inuenza A (H1N1) 2009
(0.4 percent) viruses.
Furthermore, between January and April
2012, there were 115 cases of ICU admissions
with laboratory-conrmed inuenza, includ-
ing 66 deaths. During the corresponding peri-
od in the winter u season in 2011, there were
123 cases, including 34 deaths.
While most of the deaths were among vul-
nerable groups such as the elderly, young chil-
dren and those with chronic medical conditions,
the high mortality rate underscores the need for
expanding u vaccination coverage, which may
oer protection against inuenza-related com-
plications in these patient groups.
More $ for Samaritan FundSecretary for Food and Health, Dr. York
Chow, announced recently that the govern-
ment plans to inject HK$10 billion into the
Samaritan Fund, beneing another 2,300
people. The Fund assists patients in need byproviding full or partial subsidies for self--
nanced drugs and medical items required for
medical treatment.
The 2011/12 projected expenditure of the
Fund is $295 million, representing a 30 per-
cent increase from $227 million in 2010/11. The
increase is aributable to higher demand due
to population aging, particularly an increas-
ing number of patients suering from heartdiseases. Furthermore, the government may
add some drugs and medical equipment to
the list of items the Fund currently covers,
and extend the indications of existing drugs
supported by the Fund, he added.
The projected total expenditure on non-drug items in 2011/12 is $95 million. The
projected total expenditure on drug items in
2011/12 is $200 million.
The extra funding would provide ade-
quate provision for the Funds operation over
the next 10 years, and would be closely moni-
tored, noted Chow. The major sources of its
income are government grants, reimburse-
ment from the Social Welfare Department,and donations. - NR
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13 May 2012 News
World Sepsis Day to highlight globalemergency
Rajesh Kumar
The acute care community has designated 13September 2012 as World Sepsis Day to high-light a global medical emergency that kills more
than 10,000 people worldwide every day more
than from prostate cancer, breast cancer and HIV/
AIDS combined.
Sepsis arises when the bodys response to an
infection injures its own tissues and organs. If not
recognized and treated promptly, it can lead to
shock, multiple organ failure or death. With hos-
pital mortality rates of 30 to 60 percent, sepsis
remains the primary cause of death from infec-
tion in both the developed and developing world
despite advances in modern medicine, including
vaccines, antibiotics, and acute care.
According to the Global Sepsis Alliance (GSA),
which represents about 250,000 intensive and crit-
ical care physicians around the world, the preva-
lence of sepsis has increased dramatically over
the last decade, by 8 to 13 percent annually in the
developed world alone. The GSA aributes this
trend largely due to ageing populations and the
increased use of high-risk interventions, along-
side the development of drug resistance andmore virulent varieties of pathogens.
It has also been suggested that the way sepsis
interventions are being delivered is haphazard,
with less than one in ve patients receiving ap-
propriate or adequate care according to interna-
tional guidelines.
Rapid initiation of simple, timely interven-
tions can halve the risk of dying. Early sepsis treat-
ment is cost eective and reduces hospital andcritical care bed days for patients. Unfortunately,
sepsis is still mostly overlooked and recognized
too late, said Dr. Ron Daniels, Chairman of the
UK Sepsis Group and executive director of GSA.
Professor Younsuck Koh of the department of
pulmonary and critical care medicine at Univer-
sity of Ulsan College of Medicine in Seoul, Korea,
cited an Asian observational study which showed
the basic principles of giving uid on time, taking
blood culture samples to detect pathogen, and
administering antibiotics on time were closely re-
lated to patient outcomes.
The three components could be followed
even in resource limiting countries. However, we
found that blood cultures and broad spectrum
antibiotics on time were performed in around
two-thirds of the patients, and the central ve-
nous pressure measurement as an index for uid
resuscitation was performed only around one-
third, said Koh.
The study involved 1,285 adult patients with
severe sepsis admied in 150 intensive care units
in 16 Asian countries in July 2009. The main out-
come measure was compliance with the Surviv-
ing Sepsis Campaigns resuscitation (6 hours)
and management (24 hours) components.High income countries, university hos-
pitals, intensive care units with an accred-
ited fellowship program and surgical in-
tensive care units were more likely to be
compliant with the resuscitation component.
The situation is not much beer in developed
countries. World Sepsis Day aims to change
that through education and active engagement
of physicians, decision makers and the generalpublic all over the world.
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14 May 2012 News
Bergamot orange a naturalsupplement for cholesterol control
Rajesh Kumar
An Australian cardiologist has found a
natural ally in his ght against metabolic dis-
orders an extract of the bergamot orange,
an Italian citrus fruit which has long been be-
lieved to possess heart health benets.
Dr. Ross Walker, who runs a private prac-tice in Sydney, said he has successfully used
the extract in about 700 of his registered pa-
tients who are overweight with dyslipidemia
and elevated blood sugar levels.
Within a few weeks of starting the supple-
ment, some of those patients have totally
avoided the need for statins while others
have reduced their statin dose to control dys-
lipidemia. As a bonus outcome, their bloodglucose and middle obesity have also signi-
cantly reduced, said Walker.
His ndings are consistent with those of
an unpublished clinical study conducted in
Italy involving more than 200 patients with
hyperlipidemia. In the study, 1 months sup-
plementation with bergamot reduced LDL
cholesterol by 39 percent and blood sugar by
22 percent, and raised HDL cholesterol by 41percent.
Bergamot contains extremely large
amounts of polyphenols, as compared to
other citrus species. Two of these, Brutelidin
and Metilidin, directly inhibit cholesterol bio-
synthesis in a similar way to statins and they
are not found in any other citrus derivatives,
said lead study author Dr. Vincenzo Mollace,
professor in the faculty of pharmacology at
the University of Cantanzaro in Italy.
Bergamot extract blocks the HMG CoA
reductase enzyme at a dierent level than
statins. As a result, myalgia and other side ef-
fects typically associated with statins can be
avoided because bergamot does not block the
component that depletes the muscular co-en-zyme q10, said Walker.
Bergamot extract (BergametTM) also in-
hibits cholesterol absorption in the gut, the
same way plant sterols do. Thats why I ask
my patients to take it 15 minutes before meal
twice a day, in the aernoons and evenings,
to block cholesterol absorption from food,
he said.
The unique and most important actionof bergamot, due to which cardiologists (like
me) are supporting this, is that it aects meta-
bolic syndrome as a whole: raising HDL cho-
lesterol, lowering LDL and blood sugar and
reducing arterial stiness and middle obesity.
Could patients be advised to consume ber-
gamot juice as part of a healthy diet to prevent
metabolic syndrome, rather than taking its
extract in a pill form? Walker said it is not thateasy since bergamot orange is extremely bit-
ter/sour and large amounts of its juice would
be needed to get the desired benet.
[Bergamot extract] is not a replacement
for statins. Patients who have had a heart at-
tack or have vascular disease do need to take
statins. [But] the extract can be useful in pre-
venting metabolic syndrome, correcting it in
early stages and as a supplement to reduce
statin dose, he said.
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15 May 2012 News
Omega-3 fatty acids help slow aging ofthe brainRajesh Kumar
The status of omega-3 fay acids as brainfood is well established. However, re-search now suggests a diet lacking in these
fay acids may cause brain to age faster and
lose some of its memory and thinking abilities.
The nding has prompted a study author
to recommend that physicians should remind
patients to regularly consume fay sh or
other food sources of omega-3 as part of a bal-
anced diet.
[In the study] people with lower blood
levels of omega-3 fay acids had lower brain
volumes that were equivalent to about 2 years
of structural brain aging, said lead research-
er Dr. Zaldy Tan of the Easton Center for Al-zheimers disease research and the division
of geriatrics at the University of California at
Los Angeles, California, US.
A total of 1,575 people with an average age
of 67 and free of dementia underwent MRI
brain scans for the study. They were also giv-
en tests that measured mental function, body
mass and omega-3 fay acid (comprising doc-osahexaenoic acid or DHA, and eicosapentae-
noic acid, EPA) levels in their red blood cells.
[Neurology 2012;78: 658-664].
Fay acid composition of red blood cells
(RBC) reects dietary fay acid intake aver-
aged over the RBC lifespan of up to 120 days,
whereas plasma concentrations reect intake
over only the last few days.
The researchers found that people whose
DHA levels were among the boom 25 percent
of the participants had lower brain volume
compared to people who had higher DHA
levels. Similarly, participants with levels of all
omega-3 fay acids in the boom 25 percent
also scored lower on tests of visual memory
and executive function, such as problem solv-
ing and multi-tasking and abstract thinking.
Lower DHA levels are associated with
smaller brain volumes and a vascular pat-
tern of cognitive impairment, even in persons
free of clinical dementia, concluded the re-
searchers.
It may be premature for physicians to
advise their patients to consume adequate
amounts of food rich in omega-3 specically
for their brain health, without evidence from
a large randomized control trial. But Tan said
there is already ample evidence supporting
the benets of this fay acid in cardiovascular
and overall health and such an advice couldonly be benecial.
The regular consumption of fay sh or other food sources
of omega-3 fay acids is well known to be part of a balanced
diet.
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16 May 2012 News
participants vestibular function, a measure of
how well they kept their balance. They found
that people with a 25-decibel hearing loss, clas-
sied as mild, were nearly three times more
likely to have a history of falling. Every addi-
tional 10-decibels of hearing loss increased the
chances of falling by 1.4 fold (95% CI, 1.3-1.5).
Even mild hearing loss increases riskof fallingRajesh Kumar
Adults aged 60 and older should be rou-tinely screened for hearing loss andtreated according to best practice guidelines,
according to Dr. Frank Lin, assistant professor
of otolaryngology at the Johns Hopkins Uni-
versity School of Medicine and Bloomberg
School of Public Health in Baltimore, Mary-land, US.
The advice follows research ndings that
link even mild hearing loss to a three-fold risk
of falls. Hearing loss among the elderly is al-
ready associated with a range of social and
cognitive problems, including dementia. But
the researchers feel the latest nding could
help in the development of new ways to pre-
vent falls and resulting injuries that cost bil-lions of dollars in health care.
We still do not know if treating hearing
loss can reduce falls. But hearing loss treat-
ment entails no risks and could potentially
only lead to benets for cognitive, social and
physical functioning, said Lin, adding that
hearing loss was only one of many potential
risk factors for falls.
To determine whether hearing loss andfalling are connected, Lin and colleagues used
data from the 2001 to 2004 cycles of the US
National Health and Nutrition Examination
Survey. A total of 2,017 participants aged 40
to 69 had their hearing tested and answered
questions about whether they had fallen over
the past year. [Arch Intern Med 2012;172:369-
371]
They also collected demographic informa-
tion, including age, sex and race, and tested
The nding held true even when research-
ers accounted for other factors linked with
falling, including age, sex, race, cardiovascu-lar disease and vestibular function. Excluding
participants with moderate to severe hearing
loss from the analysis also didnt change the
results.
Among the possible explanations for the
link is that people who cant hear well might
not have good awareness of their overall en-
vironment, making tripping and falling more
likely, said Lin.Another reason hearing loss might increase
the risk of falls is cognitive load, in which the
brain is overwhelmed with demands on its
limited resources.
Gait and balance are things most
people take for granted, but they are actually
very cognitively demanding. If hearing loss
imposes a cognitive load, there may be fewer
cognitive resources to help with maintaining
balance and gait, he said.
Gait and balance are ...
actually very cognitively
demanding
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White rice link to diabetes stirs debate
Rajesh Kumar
Arecent meta-analysis linking regularwhite rice consumption to signicantlyelevated risk of type 2 diabetes has stirred up
some controversy.
The analysis, conducted by researchers
from the Harvard School of Public Health
in Boston, Massachuses, US, included data
from four primary prospective cohort stud-
ies, two of which were conducted in Asia(China and Japan) and the other two in
the West (USA and Australia). [BMJ 2012;
DOI:10.1136/bmj.e1454]
The results showed that higher white rice
intake is associated with a signicantly el-
evated risk of type 2 diabetes. Assuming a
serving size of white rice of 158 grams, the
researchers estimated that the risk of type 2
diabetes is increased by 10 percent with eachadditional serving.
Dr. Daphne Gardner, associate consultant
in the department of endocrinology at Sin-
gapore General Hospital, cautioned physi-
cians against a simplistic interpretation of
the study data, saying the methods used to
quantify white rice consumption in the pri-
mary studies were very imprecise, which
made the analysis based on their pooledsummary data also imprecise.
Asian diets are known to rely on white
rice as a staple food, with some studies re-
porting white rice contributing to nearly
three-quarters of the glycemic load. Should
Western diets contain equivalent amounts of
carbohydrates (glycemic load), but of an al-
ternative form (eg, bread or potatoes), would
the same eect be seen? asked Gardner.
She suggested that the main question
ought to be: How much of the diet (ie, pro-
portion of macronutrient) should consist of
carbohydrates and what implications does
this have for the increased risk of type 2 dia-
betes?
Dr. Cho Li Wei, consultant in the depart-
ment of endocrinology at Changi General
Hospital agreed, saying the observationalnature of the study limited the ability to state
cause and eect and controlled studies were
needed to determine if white rice indeed in-
creases the risk of type 2 diabetes.
Gardner said the study had few immedi-
ate implications for physicians, patients or
public health authorities.
It should certainly not support large
scale action to change the dietary habits ofAsian populations which have been pres-
ent for centuries. In order to determine the
contribution of white rice to developing
type 2 diabetes, one would need a prospec-
tive large-scale randomized controlled trial,
with the intervention group having modied
white rice consumption. However, such a tri-
al is unlikely to happen.
The important take home message is:more ber is always benecial. And this may
take the form of increased consumption of
vegetables or less-processed foods (raw oats
rather than processed cereal). In addition,
portion control of calorie intake (whether this
is protein, carbohydrate or fat) is important in
maintaining a healthy weight and reducing
the overall risk of developing type 2 diabe-
tes, she said.
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PARTNER: 2-year study supports use ofcatheter-placed heart valves
61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
Elvira Manzano
Catheter-placed heart valves performedwell over 2 years in patients with symp-tomatic severe aortic stenosis at high risk of re-
quiring traditional open heart surgery, accord-ing to the updated results of the PARTNER*
trial.
At 2 years, the primary endpoint of death
from any cause was not statistically dierent
between patients who underwent transcathe-
ter aortic valve replacement (TAVR) and those
who underwent surgical aortic valve replace-
ment (AVR) 33.9 percent with TAVR and 35
percent with AVR, P=0.41. The rates of deathfrom cardiovascular causes also remained
comparable between the two groups (21. 4 per-
cent with TAVR and 20.5 with surgery; P=0.80).
Based on the results of the PARTNER Co-
hort A, TAVR should be considered as an alter-
native surgery with similar mortality and clini-
cal benets, said study author Dr. Susheel K.
Kodali, from Columbia University Medical
Center in New York City, New York, US.One-year results comparing TAVR with
AVR, presented at last years ACC meeting,
showed similar death rates and treatment ben-
et between the two groups. The trial was ex-
tended to determine the long-term outcomes
following TAVR and assess valve performance.
A total of 699 high-risk patients were ran-
domly assigned to TAVR (N=348) or AVR
(N=351). Patients who received TAVR eitherhad transapical or transfemoral access. The
transapical approach appeared to have a high-
er mortality rate at 2 years compared with a
transfemoral approach, however Kodali said
the study was not designed for this compari-
son.
Symptom improvement was similar in both
groups and was maintained over the course of
follow-up.
Strokes were more frequent with TAVR in
the rst 30 days, however no signicant dier-
ences were seen between the two groups at 2
years (hazard ratio [HR]=1.22, 95% CI 0.67 to
2.23; P=0.52).
Periprocedural stroke concerns aer TAVR
have diminished with longer follow-up and
TAVR hemodynamic performance was main-
tained, with no evidence of structural valve
deterioration. Kodali said. However, paraval-
vular regurgitation was more common aer
TAVR than surgery.
Interestingly, the authors found that even
mild paravalvular regurgitation was associat-
ed with increased mortality in TAVR patients.
Kodali however said the nding is not goingto dampen the enthusiasm for TAVR, instead
this will motivate us to improve on these pro-
cedures and devices.
Now we know what to x in the future.
TAVR is already comparable with surgery in
the most experienced surgeons hands. If we
can reduce these leaks, theres a good chance
we can reduce mortality with TAVR even
more, he concluded.
*PARTNER: Placement of Aortic Transcatheter Valves
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Cardiac pacing reduces syncoperecurrence
Elvira Manzano
Active pacemaker therapy can reduce ep-isodes of syncope or fainting in patientswith neurally mediated syncope (NMS), ac-cording to a recently reported study.
In the randomized controlled ISSUE- 3
study*, which involved 77 patients, 57 per-
cent of patients who had pacemakers set to
the o mode had a recurrence of syncope
within 2 years compared with only 27 per-
cent of those in the on mode (P=0.039).
The point is no therapy has been prov-
en eective for NMS syncope, said princi-pal study investigator Dr. Michele Brignole,
head of the department of cardiology, Ar-
rhythmologic Centre, Ospedali del Tigullio,
Lavagna, Italy. Now, we have evidence that
cardiac pacing works for this form of syn-
cope.
NMS, also called reex syncope, is one
of the most common forms of syncope. The
condition is characterized by peripheral va-sodilation, hypotension and bradycardia.
Brignole said reex syncope is benign re-
garding mortality but it increases the risk of
secondary trauma.
Patients in the study were >40 years old,
with severe NMS identied through an im-
plantable loop recorder (ILR) that did not
respond to more conservative interventions.
Half of them had diabetes and had a history
of injuries related to fainting. Patients were
randomized to receive dual-chamber pace-
makers with one lead in the atrium and an-
other in the ventricle that was switched on
(N=38) or o (N=39). The primary endpoint
was fainting recurrence.There was no dierence in treatment
outcomes between women and men. Proce-
dure-related complications included right
atrium lead dislodgement in two patients,
right ventricular lead dislodgement in
two patients and subclavian vein thrombosis
in one patient.
Brignole said the observed 32 percent ab-
solute and 57 percent relative syncope reduc-tion rate support the use of dual-chamber
pacemaker for relatively benign NMS. He
added that the overall strategy of using an
ILR to determine which patient needs pacing
likely contributed to the success of ISSUE-3.
We found that approximately one out of
three pacemaker patients will benet from
pacing therapy within the subsequent 2
years, Brignole said. The ecacy of pacingtherapy has been established in the study.
However, he said that the fact that pacing
is eective does not mean that it is always
necessary. Cardiac pacing should be a last
choice in highly selected patients aected by
severe NMS. He added that other patients
who suer a more benign form of NMS may
respond to less drastic treatments.
ISSUE 3*=International Study on Syncope of Uncertain Etiology 3
61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
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CT angiography reduces hospitalwaiting times
Radha Chitale
C
ardiac computed tomography (CT) an-
giograms are eective at scanning pa-
tients presenting to emergency departments
with chest pain for coronary blockages and
allows those not at risk for cardiovascular
events to go home within just a few hours, ac-
cording to the results of two US-based stud-
ies.
Up to 85 percent of chest pain cases pre-
senting to emergency departments are not
heart-related.
Ruling out the risk of heart aack or other
cardiac event typically involves a 24-hour
hospital stay plus a stress test and may in-
clude imaging. Subsequent tests can include
cardiac catheterization to determine the ex-
tent of coronary blockage. Tests can be costly,
time consuming and uncomfortable for the
patient.Discharge criteria is a less than 1 percent
risk of heart aack or heart-related death over
30 days. Risk is determined by 50 percent or
more blocked coronary arteries.
The ACRIN PA* trial randomized 1,393 pa-
tients to standard rule out care (N=462) or CT
scans (N=908). Further care was determined
by individual healthcare providers. [N Engl JMed 2012 Mar 26. Epub ahead of print]
No deaths occurred in the 640 patients
who were discharged. CT was a beer indi-
cator of coronary artery disease than stresstests (9 percent versus 3.5 percent, respec-
tively). CT was also superior to standard
care in the number of discharged patients (50
percent vs. 23 percent), median hospital stay
(18 hours vs. 25 hours) and median hospital
stay for patients whose CT or stress test re-
sults were negative (12 hours vs. 25 hours).
Since low-to-intermediate-risk patients
account for 50 to 70 percent of presentations
with a possible acute coronary syndrome,
we believe that a [CT]-based strategy can
safely and eciently redirect many patients
home who would otherwise be admied, the
ACRIN PA researchers said.
ROMICAT II*, a separate but related trial,
included 1,000 patients presenting to emer-
gency departments with chest pain random-ized to standard care or CT scan. CT scans
reduced average time spent in the hospital by
18 hours (24 vs. 36 hrs, P=0.0002).
Lead author Dr. Udo Homann, from Mas-
sachuses General Hospital in Boston, Mas-
sachuses, US, also reported 50 percent of pa-
tients were discharged within 8 hours when
assessed with CT scans. It took 28 hours todischarge half the patients with standard care.
61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
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He said the overall costs to the hospital and
patients were similar between assessment
methods and that using CT scans could help
already crowded emergency departments
beer distribute resources.
Physicians benet because they can dis-
charge many patients from the overcrowded
ER very quickly, with solid reassurance that
theyre not having a heart aack, while the
standard evaluation takes much longer to as-
sess whether the symptoms stem from block-
ages in their arteries, he said. Patients ben-
et from an earlier diagnosis and can safely
go home from the ER earlier.
*ACRIN PA: American College of Radiology Imaging Network
*ROMICAT II: Rule Out Myocardial Infarction Using Computer Assisted
Tomography II
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22 May 2012 Conference Coverage61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
Rivaroxaban tops standard PE treatment
Naomi Rodrig
Rivaroxaban, an oral Factor Xa inhibitor,has demonstrated comparable ecacyand superior safety to standard therapy for
pulmonary embolism (PE), in a large phase
III multinational study.
The EINSTEIN-PE study enrolled 4,833 pa-tients with PE, 25 percent of whom also had
deep vein thrombosis (DVT). Patients were
randomized to rivaroxaban 15 mg twice dai-
ly for 3 weeks, followed by 20 mg once daily
(N=2,419), or to standard therapy enoxapa-
rin 1.0 mg/kg for 5 days until International
Normalized Ratio (INR) was 2.0 for 2 con-
secutive days, plus warfarin or acetocouma-
rol started within 48 hours of randomization,with dose adjustment to maintain INR of 2.0-
3.0 (N=2,413). Patients were treated for 3, 6 or
12 months as deemed appropriate by the at-
tending physician. The primary ecacy out-
come was rst recurrent VTE; principal safety
outcome was rst major or non-major clini-
cally relevant bleeding. [N Engl J Med 2012;
DOI:10.1056/NEJMoa1113572]
The trial set out to show non-inferiority ofrivaroxaban and succeeded. Furthermore, it
also showed a signicant reduction in bleed-
ing, reported Professor Harry Buller of the
Academic Medical Center, Amsterdam, The
Netherlands, who is chair of the EINSTEIN
clinical trial program. Previously, the EIN-
STEIN-DVT study led to the approval of rivar-
oxaban as the only oral anticoagulant for DVT
prevention in patients undergoing knee or
hip replacement. [N Engl J Med 2010;363:499-
2510]
Rivaroxabans ecacy was highly sig-
nicant for non-inferiority, with 2.1 percent
recurrent DVT events vs 1.8 percent in the
standard therapy arm [P=0.0026], reported
Buller.
On safety measures, rivaroxaban dem-
onstrated a non-signicant trend towardsreduction in clinically signicant bleeding
with a hazard ratio [HR] of 0.9 (P=0.23). Im-
portantly, there was a 50 percent lower rate
of major bleeding, particularly intracranial
hemorrhage and retroperitoneal bleeding
(HR=0.49; P=0.0032). The biggest advantage
was seen in patients over 75 years of age,
with a HR of 0.19 for major bleeding.
Physicians want to know
about major bleeding, and
rivaroxaban was highly
signicantly superior. This was
our most astonishing nding
Bleeding rates start to separate very earlyin the treatment. Physicians want to know
about major bleeding, and rivaroxaban was
highly signicantly superior. This was our
most astonishing nding, he remarked.
These data are prey convincing. Rivaroxa-
ban is as good as standard treatment for PE
with an oral-only approach, which makes
treatment very simple. The reason people
look for alternatives to the standard treat-
ment is because its a nightmare to give, with
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23 May 2012 Conference Coverage
the subcutaneous injections and constant INR
monitoring.
Buller speculated that rivaroxaban will
likely increase cost eectiveness by reduc-
ing hospitalization time for PE. While pa-tients with DVT are usually treated outside
the hospital, with PE its a dierent psychol-
ogy, probably because the clot is closer to the
heart, he said.
He added that the investigators are plan-
ning a subgroup analysis of the 8,200 subjects
of the EINSTEIN-PE and EINSTEIN-DVT tri-als to identify a risk prole for patients who
are likely to have bleeding problems.
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Vorapaxar reduces post-MI CV mortalityrisk, but bleeding an issue
Radha Chitale
Treatment with the experimental anti-thrombotic agent vorapaxar reduced therisk of cardiovascular death and ischemic
events among patients with a history of heart
aack or stroke, but signicantly increased
the risk of bleeds and intracranial hemor-
rhage, according to a study.
This benet and risk emerged early and
continued to accrue throughout follow-up,
said researchers from Brigham and Womens
Hospital in Boston, Massachuses, US.
Vorapaxar reduced the relative risk of the
TRA 2P-TIMI 50* trial primary endpoints
cardiovascular death, myocardial infarc-
tion or stroke by 20 percent aer 3 years of
follow up. [N Engl J Med 2012 Mar 24. Epub
ahead of print]
The researchers reported the rate of the pri-
mary endpoints as 9.3 percent and 10.5 per-
cent among patients treated with vorapaxaror placebo, respectively (P
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25 May 2012 Conference Coverage61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
Elective angioplasty safe withoutsurgical backup
Elvira Manzano
Elective angioplasty, or percutaneous coro-nary intervention (PCI), performed at hos-pitals without on-site cardiac surgery units,
was no riskier than the same procedure doneat hospitals with surgical backup, according
to the C-PORT E* study.
Patient mortality rates at 6 weeks and ma-
jor adverse cardiac events at 9 months were
similar regardless of the hospitals on-site car-
diac capabilities. There were also no signi-
cant dierences in rates of bleeding and renal
failure between the two groups.
The short-term safety outcomes of elec-tive angioplasty are the same regardless of
the hospital type, said lead study investiga-
tor Dr. Thomas Aversano, associate professor
of cardiology at Johns Hopkins University in
Baltimore, Maryland, US. The study shows
that under certain circumstances, non-prima-
ry angioplasty can be performed safely and
eectively at hospitals without onsite-cardiac
surgery.Aversano and colleagues compared the
9-month outcomes of 4,718 patients who re-
ceived elective PCI at hospitals with on-site
cardiac surgery with 14,149 patients who had
the procedure at hospitals without cardiac
surgery units but which were staed with in-
terventionalists who met strict criteria for pro-
ciency and experience.
No signicant dierences in the primary
composite endpoints of death and heart at-
tack were observed between the two groups,
but there was a small increase in the need for
target vessel revascularization or repeat pro-
cedure in patients who received PCI without
surgical backup (8.5 percent vs 7 percent,
P>
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Bypass offers better survival than PCI insome patientsRajesh Kumar
Coronary artery bypass gra (CABG) sur-gery may provide higher long-term sur-vival in some patients, compared to the less-
invasive percutaneous coronary intervention(PCI) including stenting and balloon angio-
plasty, according to the largest study compar-
ing the two.
Researchers compared the health outcomes
of 86,244 CABG and 103,549 PCI patients aged
over 65 years across the US who underwent
treatment from 2004 to 2008. At 1 year post-
intervention, they found no dierence in ad-
justed mortality rates between the two groups 6.24 percent and 6.55 percent, respectively.
However, by 4 years, PCI was associated
with a higher rate of mortality than CABG
(20.80 percent vs. 16.41 percent, respectively;
risk ratio 0.79, 95% CI 0.76-0.82). Similar results
were noted for multiple subgroups and with
several dierent analytic methods.
Our study is the most general one ever
done because it uses data from across thewhole country. It is also much larger than any
other study, said lead researcher Dr. William
Weintraub, chair of cardiology at Christiana
Care Health System in Wilmington, Delaware,
US.
Some previous studies have suggested the
two treatments have similar long-term out-
comes, while others have shown beer out-
comes with bypass surgery. When both treat-
ments are an option, patients and doctors tend
to choose the less-invasive PCI. Although the
latest study found survival is beer with sur-
gery, this does not mean bypass surgery is the
best for every patient, Weintraub cautioned.
It does push the needle toward coronary
surgery, but not overwhelmingly so. Whenwere recommending coronary surgery to pa-
tients, even though it is a bigger intervention
than PCI, we can now have a lile more con-
dence that the decision is a good one.
A major limitation of observational stud-
ies such as the current one is that the groups
may not have the same level of risk, and so it
is possible that the worse outcomes in the PCI
patients were related to these patients beingsicker overall, said Weintraub.
The large number of cases allowed the re-
searchers to compare results across many
subgroups and found the data was consistent
across all subgroups, no maer what analytic
approach they used.
They found the long-term advantage for
CABG was independent of age, sex, diabetes,
renal function, and lung disease and was evi-dent even among patients whose propensity
scores were most consistent with selection for
PCI.
Survival was beer with coronary surgery
for all patient subgroups. This study should
help inform decision making concerning the
choice of revascularization in patients with
stable ischemic heart disease, he said, adding,
but there may be dierences between the
two groups that we could not account for.
61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
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Similar outcomes seen with differentCABG pump techniques
Rajesh Kumar
The largest ever randomized control trialto compare on-pump and o-pump coro-nary artery bypass graing (CABG) has foundnot much dierence in the 30-day outcomes
for both techniques. Long-term outcomes are
not yet evident.
About 4,700 patients (mean age 67.6 years)
from 79 centers in 19 countries, with coronary
artery disease, were randomized to undergo
either o-pump or on-pump CABG by an ex-
pert cardiac surgeon, experienced in at least
100 cases of the allocated technique over 2 ormore years. [N Engl J Med 2012; DOI 10.1056/
nejmoa1200388]
Primary composite endpoint including
death, myocardial infarction, stroke, or new
renal failure requiring dialysis was similar in
the two groups (9.8 percent 10.3 percent; 95%
CI 0.79-1.14 P=0.59). However, the use of o-
pump CABG (beating heart surgery) resulted
in reduced rates of transfusion, reoperationfor perioperative bleeding, respiratory com-
plications, and acute kidney injury.
The laer group also had fewer gras per-
formed and had more revascularizations (0.7
percent vs. 0.2 percent; hazard ratio 4.01; 95%
CI, 1.34-12.0; P=0.01). The co-primary out-
come involves checking for all of the above at5 years.
The ecacy of o-pump CABG is not well
established. A previous trial and Cochrane
Review have shown its benets to be only
marginal, raising the need for a randomized
trial of this magnitude to beer understand
the issue, said lead author Dr. Andre Lamy
of the Population Health Research Institute at
McMaster University in Hamilton, Ontario,Canada.
The ndings on 30-day outcomes prompt-
ed Lamy to suggest that surgeons train in
both methods and decide on which one to
use according to clinical parameters of the in-
dividual patient in question, until long term
outcomes become available.
The long-term results of the primary out-
comes and neurocognitive outcomes will havea determinant inuence on the interpretation
of this trial, he said.
61st Annual Scientific Sessions of the American College of Cardiology,
24-27 March, Chicago, Illinois, US
tive PCI into the community. The real ques-
tion is: Can these results be reproduced in
general community practice?
The study is the rst randomized controlled
trial to investigate elective angioplasty in US
community hospitals. Long-term outcomes are
expected to be released next year.
*C-PORT E: Cardiovascular Patient Outcomes Research Team Elective
>>From page 25
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24-27 March, Chicago, Illinois, US
Lowering cholesterol in childhoodreduces CVD risk later
Rajesh Kumar
High LDL-cholesterol (LDL-C) in childrenneeds to be controlled early on as a USstudy showed that doing so could be three times
beer at reducing the subsequent risk of cardio-vascular disease (CVD), than treatment with a
statin later in life.
The ndings do not suggest that everyone
should start taking statins from childhood. In-
stead, preventing high LDL-C and lowering its
raised levels through healthy diet and exercise
early on could make a big dierence to public
health in terms of CVD prevention, said lead au-
thor Dr. Brian Ference of the Wayne State Univer-sity School of Medicine, Detroit, Michigan, US.
By the time most people begin treatment to
lower their LDL-C levels, coronary atherosclero-
sis has oen been silently developing for many
decades. Researchers hypothesized that lowering
LDL-C at a younger age, or reducing prolonged
exposure to raised LDL-C, may produce even
greater reductions in their risk of CVD.
A randomized control trial (RCT) to check thishypothesis would have required monitoring a
very large number of young and healthy people
for many decades. Instead, they employed the
Mendelian RCT, which is oen referred to as the
natural RCT.
Using genetic data from over 1 million pa-
tients, they studied the eects of nine single-nu-
cleotide polymorphisms (SNPs, or single-leer
changes in DNA sequence), each of which is asso-
ciated with lower levels of LDL-C, on CVD risk.
Samples with 1 SNP were classed as the treat-
ment arm while those with no SNPs were catego-
rized as the usual care group.
Each of the nine SNPs was associated with
LDL-C levels that were lower by 2.6 to 16.9 mg/
dL and coronary heart disease risks that werelower by a relative 6 percent to 27 percent. Af-
ter adjusting the analyses for each unit of lower
LDL-C, each 38.7 mg/dL lower lifetime exposure
to LDL was associated with a more consistent re-
lationship with CVD risk, which was 51 percent
to 59 percent lower.
Combining non-overlapping data from
325,000 participants showed lifetime exposure to
lower LDL-C was associated with a 54 percent relative risk reduction of CVD per mmol/L lower
LDL-C. This eect is approximately 3-fold great-
er per unit decrease in LDL-C than that observed
during treatment with a statin started later in
life, the researchers wrote.
Previous meta-analyses have suggested that
lowering LDL-C by 1 mmol/L with statins at the
average age of 63 years reduces the CVD risk
by only 24 percent, while lowering the levels by3mmol/L through statins could achieve relative
risk reduction of up to 54 percent in the older
population.
The results of our study demonstrate that
the clinical benet of lowering LDL-C can be
substantially improved by initiating therapies to
lower LDL-C beginning early in life[and], diet
and exercise are probably as eective as statins
or other pharmacologic interventions early in
life, said Ference.
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29 May 2012 News
Study shows how smoking causes COPD
Dhenuka Ganesh
New light has been shed on how chronicobstructive pulmonary disease (COPD)develops in association with long-term
smoking.
Our ndings have important implications
for understanding the etiology of COPD and
suggest that pharmaceuticals designed to re-
duce leukocyte recruitment through the bron-
chial circulation may be a potential therapy totreat COPD, said the study authors, led by
Dr. Ryan P. Davis of the UC Davis School of
Medicine, Davis, California, US.
Their research revealed that tobacco smoke
exposure stimulates neutrophils to migrate
from the bronchial blood vessels, due to the
production of adhesion molecules and che-
mokines, and accumulate in the lung tissues.
Although neutrophils help repair tissues,excessive numbers of activated neutrophils
can release enzymes that kill cells and accel-
erate inammation.
In this study, a highly reproducible animal
model of COPD was used to show that the
equivalent of approximately 10 years of one-
pack-a-day smoking completely damages the
bronchial airways by accelerating inamma-
tion, obstructing airow, and reducing nor-mal lung function. [PLoS One 2012;7:e33304.
Epub 2012 Mar 21]
The researchers studied rats having a ge-
netic defect that made them react to smoke
exposure much like humans with smoking-re-
lated diseases. The animals developed all the
physiological and anatomical traits of COPD.
A smoking machine was used to auto-
matically load, light, and pu on cigarees,
and the rats were exposed to amounts that a
two-pack-a-day smoker would be exposed to,
for 6 hours a day, 3 days a week.
Aer 4 weeks, their physiological changes
reected those of a 10- to 20-year smoker with
complications of wheeze and cough and re-
duced respiratory function. Aer 12 weeks, they
were reective of a 30- to 40-year smoker hav-
ing severe limitations in breathing and COPD.The UC Davis team is now testing whether
statin drugs may prevent COPD development
in this model. The model appears to be ideal
for screening drugs to treat early COPD, but
the ultimate test comes when a treatment is
transitioned from the lab to COPD patients,
said the lead author, Dr. Benjamin Davis.
Our primary goal is to save lives.
According to the WHO, COPD is thefourth leading cause of death worldwide. In
India, around 15 million people suer from
COPDthis number is expected to increase.
Dr. Aloke Gopal Ghoshal, director of the Na-
tional Allergy Asthma Bronchitis Institute, Kol-
kata, India, stressed the importance of COPD
management and treatment. [In India], people
who are more exposed to biomass fuel and
smoke are at a greater risk of having COPD
this number is around 578 million.
COPD is the fourth leading cause of death worldwide,according to the WHO.
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30 May 2012 News
Potential new target identified fortreating infectious diseases, cancer
Dhenuka Ganesh
Anovel T-cell activation pathway thoughwhich dendritic cells become highly spe-cialized to ght Mycobacterium leprae, the
causative agent of leprosy, may be a potential
therapeutic target for a range of infectious dis-
eases and cancer, according to new research.
Dendritic cells, which deliver key informa-tion about an invading pathogen for T-cell ac-
tivation, have been known to be important for
eliciting a strong immune response and their
numbers at the infection site are positively
correlated with this robust reaction. However,
it was poorly understood how dendritic cells
become more specialized to address specic
types of infections.
The research found that a protein calledNOD2 triggers the cell-signaling molecule
interleukin-32 that induces general immune
cells monocytes to become specialized
information-carrying dendritic cells. [Nat Med
2012 Mar 25;18:555-63]
This is the rst time that this potent infec-
tion-ghting pathway with dendritic cells has
been identied, and demonstrated to be im-
portant in ghting human disease, said thestudys lead author Mirjam Schenk, postdoc-
toral scholar, division of dermatology, David
Geen School of Medicine at UCLA, Los An-
geles, California, US.
The scientists used monocytes from the
blood of healthy donors and leprosy patients
and incubated the cells with M. leprae or spe-
cic parts of the bacterium known to trigger
NOD2 and TLR2, both associated with im-
mune system activation.
The objective was to investigate how these
proteins might trigger mechanisms that ac-
tivate dierent immune receptors that rec-
ognize specic parts of the microbe in an
infection. They found that the NOD2 inter-
leukin-32 pathway was the most eective and
caused the monocytes to dierentiate into
dendritic cells.
The team also studied the gene expressionproles of the protein-triggered pathways
and then examined how the monocytes of lep-
rosy patients responded to NOD2. The pro-
tein induced the monocytes to develop into
dendritic cells in tuberculoid leprosy, a mild-
er infection that is more easily contained. The
NOD2 pathway was inhibited and could not
be activated in lepromatous leprosy, which is
more serious and causes widespread infec-tion throughout the body.
We were surprised to nd the high poten-
cy of the dendritic cells in triggering certain
specic T-cell responses, which may be useful
in developing new therapeutic strategies for
infectious diseases and cancer, said senior
investigator Dr. Robert Modlin, UCLAs Klein
professor of dermatology and chief of derma-
tology at the Geen School of Medicine.Modlin added that leprosy is a good model
to study immune mechanisms in host defense
since it presents as a clinical spectrum that
correlates with the level and type of immune
response of the pathogen.
The next stage of research will involve try-
ing to further understand how to manipulate
the innate immune system to induce a potent
immune response in human infections and
possibly for cancer immunotherapy as well.
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31 May 2012 News
Breast cancer survivors can learn tohandle hot flushes, night sweats
Radha Chitale
Cognitive behavioral therapy (CBT) is ef-fective at reducing the hot ushes andnight sweats (HFNS) that are common fol-
lowing treatment for breast cancer, according
to a study.
HFNS, which the study researchers re-
ported aect up to 85 percent of women aer
breast cancer treatment, are sources of dis-
tress and negatively impact patient quality of
life.
Hormone replacement therapy for HFNS,
used among aected women who are meno-
pausal, is contraindicated or undesirable in
cancer patients. Previous research has shown
reductions in HFNS with paced breathing and
the researchers reported pilot trials showed
promise for CBT.
The improvement in social functioning
aer CBT is relevant because women report
nding hot ushes especially dicult to deal
with at work and in other social situations,
the researchers said. Additionally, group
CBT provided sustained benets to depressed
mood and sleep and some improvements indimensions of quality of life.
Women from breast clinics in the UK who
had at least 10 HFNS episodes per week af-
ter breast cancer treatment were random-
ized to receive usual care (N=49) or usual
care plus one 90-minute session per week
of group CBT (N=47). [Lancet Oncol 2012
Mar;13:309-318]
Usual care included follow-up visits tooncologists or clinical nurse specialists ev-
ery 6 months and as needed, telephone sup-
port from a cancer survivorship program,
information leaets, and advice about
HFNS and treatment options, including
symptoms management, paced breathing
and relaxation.
The CBT program was based on the caus-
al and maintaining factors of HFNS, includ-
ing anxiety, stress, embarrassment, negative
beliefs and catastrophic thoughts, and the
resultant behaviors, which can impact pa-
tient outcomes, such as avoidance activities.
Women receiving CBT spent 6 weeks in
structured, interactive group classes where
they were given information about the
physiology of HFNS, taught paced breath-
ing, relaxation techniques and behavioral
strategies to manage HFNS.
The weekly plan included discussions on
topics including handling HFNS, the role of
stress, and what cognitive factors might con-
tribute to it. Women were given the opportu-
nity to describe their own experiences with
HFNS as a result of breast cancer, their trig-gers and outline their treatment goals.
CBT signicantly reduced HFNS aer 9
weeks and the results were maintained at 26
weeks compared with usual care (adjusted
mean dierence in HFNS problem rating [1-10
scale] -1.67 and -1.76, respectively; P
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32 May 2012 News
reuptake inhibitors (SSRIs) or gabapentin
that result in moderate reductions in HFNS
frequency about 37 percent across trials,
the researchers reported, but with few im-
provements in quality of life.We do not know whether HFNS were
caused by breast cancer treatments or
whether women were naturally meno-
pausal when they had breast cancer, the
researchers said. However, treatment op-
tions are still restricted for these women
the most cost eective method of delivering
the group CBT would probably be to in-clude it as part of survivorship support pro-
gram, delivered by trained and supervised
breast-care nurses.
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33 May 2012 News
Minimally invasive technique safe,effective for ruptured aneurysms
Dhenuka Ganesh
Aminimally invasive interventional radi-ology treatment for ruptured abdominalaortic aneurysms (AAAs) resulted in signi-
cantly fewer hospital deaths aer treatment
as compared to open surgery, according to a
new study.
People with peripheral arterial disease
are at risk of an aneurysm, which is a weak-
ening and abnormal bulging of a major ar-
tery. Once this area of bulge ruptures, this can
lead to fatal internal hemorrhage, explained
study co-author Dr. Prasoon Mohan, from the
department of diagnostic and interventional
radiology at Saint Francis Hospital in Evan-
ston, Illinois, US.
Once an AAA reaches a particular size,
treatment is recommended to prevent its rup-
ture. Conventional open surgery involves
making a large abdominal incision and then
replacing the dilated portion of the aorta with
a synthetic blood vessel.
In contrast, the less-invasive endovascular
aneurysm repair (EVAR) technique involves
a small incision made in the groin for a thinwire catheter to be guided through the femo-
ral artery to the dilated aorta. Once in place,
a stent gra compressed into the catheter is
opened up and the edges of the stent push
against the aortic wall, holding it in place.
Blood ows through the stent gra instead of
the abnormally dilated aorta and prevents it
from rupturing.
In their retrospective study, the researchersmined the National Inpatient Sample data-
base for all cases of ruptured AAA from 2001
to 2009, treated by one of the two techniques.
Of the 32,069 patients who received open
surgery, 39.7 percent died in the hospital,
compared with 28.2 percent of the 6,790 EVAR
patients (P
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34 May 2012 In Pract ice
Managing acute otitis media:Strategies for GPs
Dr. Eng Soh Ping
Consultant ENT Surgeon
Ascent Ear Nose Throat Specialist Group
Mount Elizabeth Medical Centre
Singapore
Disease of childhood
Acute otitis media (AOM) inammation
of the middle ear is the second most com-
mon disease of childhood aer upper respi-
ratory tract infection (URTI). Most children
have at least one or two episodes during
childhood; many have repeated episodes
with the peak incidence occurring between
ages 2 and 5.
Obstruction of the Eustachian tube is the
most important antecedent event linked to
this condition. Children are particularly sus-
ceptible because they have shorter and more
horizontal Eustachian tubes than adults
which are not fully developed and are more
dicult to drain. With age, however, part of
the tube ossies to bone and the horizontal
angle descends, increasing the downward
ow of uid.
A grommet tube in position.
A bulging erythematoustympanic membrane.
Otitis media with eusionresolves without surgery.
Surgery takes only 10 minutes but recovery takes a few days.
What causes
AOM?
Otitis media is
caused by viraland bacterial in-
fections. The most
common bacte-
ria responsible are Streptococcus pneumoniae,
Streptococcus pyogenes, Staphylococcus aureus
and Moraxella catarrhalis. Among older chil-
dren, the most common cause is Haemophilus
inuenzae.
The vast majority of AOM episodes are
We cannot predict which
patients will go on to develop
complications. Thus, we should
be aggressive, but a lile cautious,
when managing AOM
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35 May 2012 In Pract ice
triggered by URTIs. Eustachian tube dysfunc-
tion is a major risk factor. If the Eustachian
tube becomes blocked, uid can build up and
lead to infection. Other risk factors for acute
ear infections are aending daycare, changesin altitude or climate, recent ear infection and
genetic factors. The childs position during
bole-feeding, for example lying down, also
predisposes the child to AOM. For this rea-
son, breast-feeding position semi-Fowlers
may be good for normal Eustachian function.
Signs and symptoms to watch out for
When the middle ear which is normally
sterile becomes acutely infected, pressure
builds up behind the eardrum, resulting in
otalgia. The tissues surrounding the tubes
swell and uid accumulates in the middle ear.
Pyrexia, with or without co-existing URTI, is
a common symptom in children of any age.
Aside from earache, older children may com-
plain of fullness in the ear and conductive
hearing loss, which is usually transient.
In young children, complaints of ear pain
can be muted and only represented by crying,
irritability and sleeping or feeding dicul-
ties. Severe infections or untreated cases may
cause the eardrum to rupture, causing the pus
to drain from the middle ear to the ear canal.
The condition usually resolves with phar-
macological treatment. However, what weare worried about are those cases that do not
rupture and have become complicated. More
commonly, it would lead to mastoiditis which
requires emergency surgery. Untreated, the
infection can spread to surrounding struc-
tures, aecting the brain and the facial nerves.
Diagnosing AOM
The presence of the above symptoms, com-bined with a complete clinical history and
accurate visualization of the tympanic mem-
brane may lead GPs to the diagnosis of acute
otitis media one of the three presentations of
otitis media (OM), the other two being recur-
rent otitis media and otitis media with eu-sion (OME) or glue ear.
A direct examination of the middle ear
with an otoscope will reveal erythema, bulg-
ing and apparent opacity. The normal tym-
panic membrane moves in response to pres-
sure changes. In AOM, mobility is reduced or
absent with pneumatic otoscopy. An accurate
clinical diagnosis is possible in most cases,
but this is a challenge to physicians as the ca-
nal is small and the view may be obscured by
earwax. Crying may also distend the small
blood vessels in the eardrum, mimicking the
redness associated with AOM.
Another useful but lost skill among physi-