Medical Tribune May 2012 HK

7/28/2019 Medical Tribune May 2012 HK

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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


2/53

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


8/53


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


9/53


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


10/53


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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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


12/53


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


13/53


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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.


15/53

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.


16/53

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.


17/53

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


18/53

17 May 2012 News

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.


19/53

18 May 2012 Conference Coverage

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


20/53


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




21/53


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.




22/53


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


23/53

22 May 2012 Conference Coverage61st Annual Scientific Sessions of the American College of Cardiology,


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


24/53


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.


25/53


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


26/53



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>


27/53


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.




28/53


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.



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


29/53



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.


30/53

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.


31/53

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.


32/53

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


33/53

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.


34/53Website: www.ensure.com.hk


35/53

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


36/53

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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


38/53

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-

Documents

Medical Tribune May 2012 HK