Medical Tribune April 2013

8/11/2019 Medical Tribune April 2013

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April 2013

www.medicaltribune.com

Link between HRT and

breast cancer disputedDaring to dream

FORUM

RESEARCH REVIEWS

NEWS

CONFERENCE

Asian CV, diabetes risk

profle unique

Osteoporosis prevention should be

started early

Pandemic u vaccine and

epileptc seizures: No link


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2 April 2013

Osteoporosis prevention should be started

early

Pank Jit Sin

Bone mineral density (BMD) peaks duringadolescence, hence this is the best time toaccumulate calcium, says a specialist.

Discussing various studies on bone healthand its associated factors, Professor NikhilTandon, of the department of endocrinology

and metabolism, All India Institute of MedicalSciences, New Delhi, India, said peak BMD atcertain important sites is achieved by the endof the second decade of life. Thus, pubertalyears are critical for bone mass accumulation.

Speaking at the 3rd Asia-Pacic Osteopo-rosis Meeting held in Kuala Lumpur, Malay-sia, recently, Nikhil said: Eighty percent ofpeak bone mass is achieved from birth to ad-olescence. The annual increase in BMD and

volumetric BMD is most marked in femalesat time of menarche and in males between 13and 17 years of age. [J Clin Endocrinol Metab1992;75:1060-1065, Bone Miner1993;23:171-182]

Physically active people have signicantlyhigher mineralization rates compared withtheir sedentary counterparts, he said. A study

by Jones and Dwyer revealed that sports par-ticipants have around 4 percent higher BMD

in their femoral neck and lumbar spine com-pared with those who did not exercise. [J ClinEndocrinol Metab1998;83:4274-4279] However,it was also noteworthy that increasing bonemass through physical activity wanes aer pu-

berty. [Acta Paediatr 1996;85:19-25]Calcium is the most touted nutrient for

healthy bones. Nikhil said most cross-section-al studies have identied a positive correla-tion between dietary calcium and childhoodBMD. The threshold for calcium intake is be-tween the ages of 9 and 17, with a daily intake

of 1,500 mg [Am J Clin Nutr 1992;55:992-996]Peak calcium accretion rates are achieved ingirls aged 12.5 years and in boys aged 14. Sim-ilarly, high calcium intake also has a protec-tive eect against fractures in adolescents.

Looking at intervention studies utilizing

exercise, calcium, vitamin D and other for-tied foods, he said the eects are very ap-parent, especially in populations which werepreviously undernourished. Unfortunately,these benets are not always sustained onceintervention is stopped. He reiterated that theoutcomes of intervention studies oen de-pend on the baseline characteristics.

If you look at the outcome of the same

studies on a population in developed countrieswith adequate macronutrition, then the likeli-hood of such a study bringing benets is goingto be very low. Conversely, the same inter-vention studies using the same macronutrientssuch as calcium and vitamin D carried out ina developing country with poorer nutritionalstatus would yield more pronounced benets.

But Nikhil said the transition from re-search projects to public health policy has yetto commence, although that is arguably themost important reason for research.

Studies have revealed that 80 percent of peak bone mass is achieved beforeadolescence.


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3 April 2013

Predictive genetic testing not advised

Radha Chitale

Ajoint policy statement from the AmericanAcademy of Pediatrics and the AmericanCollege of Medical Genetics and Genomics

denitively recommends against genetic test-

ing for inherited adult-onset diseases during

childhood.

The organizations argue that unless inter-

ventions during childhood can reduce mor-bidity or mortality, such predictive genetic

testing can have signicant medical, psycho-

logical, and social implications, not only for

the minor but also for other family members.

[Pediatrics2013;131:620-622]

The authors note that genetic testing and

screening should always be done in the con-

text of the best interest of the child and togeth-

er with professional guidance and counseling.This position prioritizes the childs auton-

omy and privacy interest over his/her parents

desire to know, said Dr. Calvin Ho, assistant

professor at the Centre for Biomedical Ethics

at the National University of Singapore.

Similar recommendations were made

in a 2005 report by Singapores Bioethics

Advisory Commiee, Ho said.

In the US, newborn screenings for metabol-ic, hematologic and endocrine abnormalities

are common and these abnormalities can be

treated early.

But advances in genetic testing and screen-

ing technology as well as increased consumer

interest and the rise of home testing kits high-

lighted the need for clarity about when and if

to conduct further tests on young children.

Previously, experts have pointed out that

knowledge of adult-onset diseases for which

there is no childhood intervention could com-

promise the child through diversion of family

resources, stigmatization, childs loss of self-esteem and discrimination by family or insti-

tutional third parties such as schools. [JAMA

1994;272:875-881]

Direct-to-consumer and at-home genetic

test kits, such as 23andMe, are highlighted in

the position paper as particularly problematic

as they lack professional oversight for accura-

cy and interpretation and counseling.

The policy statement makes an exceptionto their recommendation in cases where di-

agnostic uncertainty poses a signicant psy-

chosocial burden, particularly when an ado-

lescent and his or her parents concur in their

interest in predictive testing.

These exceptions are important for their

recognition of the critical role of the family as

caregivers, Ho said, although he noted that

in most cases, deferring genetic testing is ethi-

cally and legally sound.

Genetic screening should only be done in the best interests of the child, sayexperts.


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4 April 2013 Forum

Daring to Dream

A doctor recounts his humble beginnings and his determination to succeed.

Dr. Low Lee Yong has mastered chang-

ing cannot into can. In a new memoir

called I Dare to Dream: Make Pos-

sible the Impossible, Low, the son of a goods

hawker and homemaker, relates his child-

hood in a Bukit Timah kampong village in the

1970s and his journey to become a physician

and eventually founder and CEO of the man-

aged care organization MHC Asia Group,

which links over 1,000 clinics in Singapore

and Malaysia through a virtual administra-

tive system.

Despite his mothers urging to become a

teacher, the sight of people seeking help from

doctors in white coats impressed Low enough

to choose medicine as a career, in spite of lile

encouragement from teachers and poor English

and Mandarin language skills. Lows book oers

brief snapshots of the ups and downs of start-

ing his own practice in Ghim Moh, expand-

ing a medical conglomerate and a short but

intense bout in politics. Now, Low, 49, spends

the majority of his time overseeing MHC and

will be writing more, including an account of

MHCs founding and a book of life lessons told

through jokes. Radha Chitale sat down withLow to discuss his story.

Growing up poor had a consistent impact on

you as you struggled for success, especially

through school. What aspects of that life are

you glad to have le behind and what do you

wish you could have kept?

In the early 70s, growing up in the kampong,

life was simple, there was no technology, ev-erybody was happy and until you see people

who are rich you dont

know that you are poor.

Because its a simple

life, running around with-

out slippers, plucking

fruits, chasing animals,

innovating and improvis-

ing toys. But its dicult in

the sense that every day there are lots of things

to do like washing clothes, tending the farm,

scooping sewage, chopping wood, and thats

not easy.

But it was not complicated like modern

life where you have to worry about a thou-

sand and one things, reply to emails and

have lots of responsibility. Its a tough life

but you kind of miss it because its a simple

life as well.

You took a lot of big nancial risks through-

out your career, sometimes without a safety

net. What drove you to jump into big invest-

ments like that?

When you have nothing to lose, you really

have nothing to lose. I wasnt in to get any-

thing in the rst place, just to try to exploreand learn, not knowing that I was taking risks.

For example, I didnt realize I was taking loans

at 20 percent interest to buy out my [S$30,000

service] bond. I just wanted to get out.

When you are quietly thinking about it, yes,

the amount of money borrowed is huge and to

owe the bank S$30,000 and later on much more

is quite scary. I think I knew it was a big thing

but I didnt feel the risk because the ideas ofinterest and cost didnt really cross my mind.

Dr. Low Lee Yong


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5 April 2013 Forum

If you ask me, it was partly ignorance, partly

guts and partly determination.

If I were to do it now, of course I would take

risks but calculated risks. I know how to get in,

how to get out and when to get out. I learnedthat, whatever you want to venture into, think,

what is the worst-case scenario and can you

live with it? If you can, then ok, go for it.

You converted to Christianity during medical

school and faith plays a large role in your life.

How do your faith and your medical training

inform each other?

As a doctor you see life and death situations.

Obviously we all know that we dont live for-

ever so theres this question of where are you

going. So if you can get answers seled early

in your life and in your career then its much

easier to handle life and death situations.

As a business person, my faith helps me in

my value systems. Many times you might be

tempted to do things on the borderline when

there is no straightforward right or wrong

and your faith has to come in and tell you to

do right, not what only benets you or your

company. I dont think I ever got into busi-

ness to get rich. I got into business because its

a game... youre going into the unknown and

creating things and making a dierence.

Why did you write this book?People kept asking me, why did you start

MHC? And Cecilia [Tan, Chairman of MHC

Asia Group] has been pestering me to write

it because she knows what I went through. I

thought, yes, I should write it because if I dont

share the lessons I learned then other people

cannot benet from it.

I want to tell students, look it doesnt mat-

ter what your teacher says, its not the end of

the world, you can make a dierence and you

can prove they are wrong. If you have passion

you can go forward. And I want to tell teach-

ers that look, your words do make a dier-

ence in our lives. Its not true that what you say

comes in one ear and out the other because as

it goes through, the brain can get damaged or

inspired.

At any point, did you concede that your

mother may have been right and you should

have been a teacher?

To a certain extent, my mother is absolutely

right. I should have been a teacher because Ind myself educating everyone now with my

stupid mistakes! All the things I ever learned, I

educate others by sharing my stories. You need

to be a great educator to motivate and inspire

patients to take charge of their health. To me,

part of health education has to be when people

can remember a story and they enjoy it.


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6 April 2013 News

Double dose of flu vaccine may benefit HF

patients

Rajesh Kumar

Adouble dose of inuenza vaccine may

improve the immune response in

patients with heart failure (HF), a

pilot study has shown.

Flu infection causes increased morbid-

ity and mortality in those with HF and such

patients exhibit reduced antibody responses

to inuenza vaccine.

To determine whether doubling the dose

of the vaccine would mount more vigorous

humoral immune responses, 28 patients with

HF were randomized to receive either double-

dose (30 mg/strain) or standard single-dose

(15 mg/strain) inuenza vaccine. Antibody

production was assessed by hemagglutina-

tion inhibition assay (reported as log hemag-

glutination units) prior to, at 2 to 4 weeks, and

at 4 to 6 months following vaccination. [Eur J

Heart Fail2013; doi:10.1093/eurjhf/hfs207]

Baseline antibody titers between double-

dose and single-dose did not dier signicant-

ly. At 2 to 4 weeks, double-dose hemaggluti-

nation unit changes were signicantly higher

than those of single-dose (3.3 vs 1.6 for A/H3N2,

p=0.001; 1.9 vs 1.1 for A/H1N1, p=0.009; and 1.7

vs 1 for B-type, p=0.02). At 4 to 6 weeks, therewere no dierences in titers in any of the virus

types between treatment groups and, although

titers decreased, levels remained above the

seroprotective threshold.

However, the data are preliminary and

larger clinical trials are being planned to

conrm the results, said study co-author Dr.

Orly Vardeny, associate professor of pharma-

cy and medicine at the University of Wiscon-

sin-Madison in Wisconsin, US.

What we do know is that patients with

heart failure mount a weaker immune

response to inuenza vaccine, which may

leave them less protected during inuenza

season. However, it is premature for clini-cians to alter vaccine dosing strategies based

on this study alone, concluded Vardeny.

Dr. Teo Swee Guan, cardiologist at Raes

Heart Centre in Singapore, agreed, adding

that the study is still important because it sets

the stage for a larger trial to evaluate if double

dose translates into beer clinical outcome.

From heart failure patients point of view,

the most important point is to have yearlyinuenza vaccination.

Patients with HF are known to mount a weaker immune response to theinuenza vaccine.

The study is ... important because

it sets the stage for a larger trial to

evaluate if double dose translates

into beer clinical outcome


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7 April 2013 News

Exercise plays positive role in hypertension

Leonard Yap

We have always known that exercise isgood for preventing cardiovasculardisease and hypertension, but the reason for

this and the amount of exercise needed to

elicit a positive response on blood pressure

(BP) have not been clear, says an expert.

Exercise has been shown to reduce sys-

tolic and diastolic BP, increase serum HDLcholesterol and decrease serum triglycer-

ides, said Dr. Mohd Nahar Azmi Mohamed,

a consultant sports physician at University

Malaya Medical Center, Kuala Lumpur. [Am

J Cardiovasc Dis 2012;2:102-10, Sports Med

2000;30:193-206]

Exercise has also been shown to reduce

total body and intraabdominal fat, increase

insulin sensitivity and reduce platelet adhe-siveness and aggregation, he said. [Am J Car-

diovasc Dis2012;2:102-10] A meta-analysis of

54 randomized clinical trials found a reduc-

tion in systolic BP of an average 3.84 mmHg

and diastolic BP of 2.58 mmHg when patients

were randomized to perform aerobic exer-

cise. [Ann Intern Med2002;136:493-503]

Mohd Nahar proposed a mechanism of

how exercise aects BP lowering. He saidexercise decreases catecholamines and total

peripheral resistance, improving insulin sen-

sitivity, which also alters vasodilatation and

vasoconstriction of blood vessels. [Pathophys-

iology2003;10:47-56]

Exercise is the cornerstone therapy for pri-

mary prevention, treatment and control of

hypertension. Optimal training frequency,

intensity, time and type (FITT) should be bet-

ter dened and individualized to optimize

BP lowering, he said.Mohd Nahar recommended the following

exercise regimens for hypertensive patients:

Frequency: on most, preferably all, days

of the week.

Intensity: moderate (dened as 40 to 60

percent maximal oxygen consumption [VO2

max]) ie, brisk walking or gardening.

Time: 30 minutes of continuous or accu-

mulated physical activity per day. Type: primarily endurance physical ac-

tivity supplemented by resistance exercises

ie ,walking at the supermarket and carrying

shopping bags lled with groceries. [www.

who.int/dietphysicalactivity/physical_activity_

intensity/en/index.html. Accessed on 20 March]

He said studies have shown that low-to-

moderate training is just as ecient in lower-

ing BP as high intensity (more than 70 per-cent VO2 max) cardiovascular exercise. [J

Hum Hypertens 1997;11:641-649] The tness

level of the individual plays a central role in

determining optimal intensity and should be

tailored to the patient.

He cautioned that special considerations

should be taken with patients on antihy-

pertensive medications, particularly beta-

blockers and diuretics. These medicationsimpair the ability to regulate body tempera-

ture during exercise and may lead to undi-

agnosed hypoglycemia. People using these

medications should be educated on the signs

and symptoms of heat illness, the role of ad-

equate hydration and proper clothing to fa-

cilitate evaporative cooling.

They should also be educated on the im-

portance of decreasing exercise time and in-

tensity during periods of high temperature


8/32

8 April 2013 News

and humidity. Beta-blockers can substantial-

ly alter submaximal and maximal exercise

capacity, particularly in those with myocar-

dial ischemia, he said.

Many hypertensive patients are over-weight, with a body mass index (BMI) of 25

to 29.9 kg/m2or obese, BMI of more than 30

kg/m2. Exercise programs must emphasize a

daily caloric expenditure of more than 300

kcal, coupled with reduced energy intake.

This can be accomplished with moderate

intensity prolonged exercise such as walk-

ing. A combination of regular exercise and

weight loss should be eective in loweringBP, he added.

Mohd Nahar was speaking at the Malay-

sian Society of Hypertensions 10th Annual

Scientic Meeting 2013 in Kuala Lumpur.

Tofacitinib reduces RA symptoms, haltsjoint damage

Rajesh Kumar

Tofacitinib, a janus kinase (JAK) enzymeinhibitor, improved disease activity andhalted joint damage in rheumatoid arthritis

(RA) patients who did not respond to metho-trexate in a phase III trial.

JAK enzymes are found in white blood

cells and help to regulate the immune sys-

tem. Researchers randomized 797 patients in

a 4:4:1:1 ratio to receive either 5 mg (n=321)

or 10 mg (n=316) of oral tofacitinib twice

daily (BID), or placebos to both doses (n=81

and n=79, respectively). [Arthritis Rheum

2013;65:559570]We [examined] tofacitinib as a disease-

modifying antirheumatic drug for its abil-

ity to modulate the immune system in those

with RA, said lead researcher Dr. Dsire

van der Hede from Leiden University Med-

ical Center in the Netherlands.

With a mean age of 53 years, 85 percent

of the participants were female (54 percent

non-Caucasian). They had RA for an aver-

age of 9 years. Those who did not respond

to placebo were advanced to tofacitinib at

3 months while the remaining placebo par-

ticipants were advanced to tofacitinib at 6

months.

Results from a planned 12-month interim

analysis from the 24-month trial showed that

the drug is eective in preserving joint struc-

ture in patients with moderate to severe RA

who had an inadequate response to metho-trexate therapy. The American College of

Rheumatology 20 percent (ACR20) response

rates for tofacitinib 5 mg and 10mg BID at

6 months were higher than that for placebo

(51.5 percent and 61.8 percent, respectively,

versus 25.3 percent; both p


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9 April 2013 News

month 6 (co-primary endpoint) and month 12.

Patients treated with tofacitinib at both 5 mg

and 10 mg BID doses displayed less progres-

sion of joint erosion and joint space narrowing

compared with placebo at 6 and 12 months.Change in the joint space narrowing score

was statistically signicant at month 12 for

the tofacitinib groups versus placebo. Re-

searchers also reported that the proportion

of patients with no radiographic progression

in the tofacitinib groups was signicantly

greater compared with placebo.

Analysis conrms previous results that

tofacitinib is eective in treating RA symp-

toms and reducing the rate of joint damage.

Our ndings provide the rst evidence thattofacitinib reduces the progression of struc-

tural damage in RA patients with active dis-

ease, concluded Dr. van der Hede.

Tofacitinib is the rst oral JAK inhibitor to

have been approved by the US FDA for the

treatment of moderate to severe RA.

Fast food linked to severe asthma,

allergies in kids

Monika Stiehl

Frequent fast food consumption may be

linked to severe asthma, allergies andeczema in children and adolescents,

according to a recent international study.

The ndings could have major public health

signicance owing to the rising consumption

of fast foods globally, if they turn out to be

causal, said researchers from participant

countries including Singapore, New Zea-

land, the UK, Spain, Australia and Germany.

The study included data from more than319,000 teenagers aged 13 to 14 years and

more than 181,000 children aged 6 to 7 years

with allergies or asthma who participated in

the large International Study of Asthma and

Allergies in Childhood (ISAAC).

The teens and parents of the younger

children completed questionnaires about

the symptoms and severity of their allergic

diseases, asthma, rhinoconjunctivitis and

eczema, and about their weekly diet, fo-

cusing on how oen they consumed fruits,

vegetables and fast foods like hamburgers in

the past 12 months. [Thorax2013;68:351-360]

Thirty-nine percent of adolescents and 27

percent of younger children were more likely

to have severe asthma if they ate hamburgers

and other types of fast food more than three

times a week. There was also an increased

risk for severe eczema and rhinoconjunctivi-

tis.

Fast food may exacerbate asthma and eczema.


10/32

10 April 2013 News

Conversely, diets containing fruits seemed

to be protective against allergic disease,

according to the study. Eating fruits three

times or more per week reduced the symp-

tom severity for all three conditions amongchildren by 11 percent and reduced symp-

tom severity for asthma and rhinoconjuncti-

vitis among teens by 14 percent. The data

of Singapore follow the trend, said Profes-

sor Lee Bee Wah of the Department of Pae-

diatrics, Yong Loo Ling School of Medicine,

National University of Singapore, who has

been involved as an investigator in this trial.

Eating more fast food instead of fruits

and vegetables is part of globalization and

Western lifestyle and there is likely to be an

increase also in Singapore, Lee added.

Fast food contains high levels of saturat-

ed and trans fay acids, which the authors

note are known to aect immunity. Likewise,

fruits are rich in antioxidants and other ben-

ecial compounds.

Although the authors mentioned ham-

burgers specically in their report, since theyare one of the most common fast food items

sold around the world, overall the study did

not dierentiate between dierent types of

fast food.

Fast food was the only food type associ-

ated with asthma and allergies across all age

ranges and countries.

Such consistency adds some weight to

the possible causality of the relationship,

the researchers said. But nevertheless,

more research would be needed to discover

whether fast food is denitely a problem.

The advice for eating healthily is

reinforced with these results, Lee said.

Memory-enhancing medications beingmisused in US

Laura Dobberstein

US doctors have called for an end to theo-label use of memory-enhancingmedications, like the ones used to treat aen-tion-decit-hyperactivity disorder (ADHD),

in healthy individuals.

Evidence suggests that o-label prescrip-

tions for neuroenhancement and prescription

drug misuse are gradually increasing in both

adult and pediatric populations, said the

study authors led by Dr. William Graf from

the Yale School of Medicine, New Haven,

Connecticut, US.

Parental and societal pressures alongside

vague guidelines of appropriate medication

use create a challenge for medical profession-

als when deciding whether neuroenhance-

ment is needed.

While there is a growing awareness lead-ing to an increase in ADHD cases and diagno-

sis, other factors such as inadequate exercise,

decient sleep and excessive use of television

and computers have also been linked to a rise

in neuroenhancement medication use. Pres-

sure to misuse the medications in order to

perform is also a challenge.

The authors noted that medical profession-

als have an obligation to prevent the misuse

of medication. They suggested that physi-


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11 April 2013 News

cians consider the possibility that requests for

this type of medication may be due to other

medical, social and psychological reasons.

Treatment of children with neuroenhance-

ment requires extra considerations not pres-ent when dealing with adults.

While adults have the ability to make im-

portant medical decisions, children do not

have these capabilities and rely on parents

and doctors to keep their best interests in

mind.

Long-term health and safety must also be

considered. The eect of neuroenhancement

medication on a childs cognitive develop-

ment is not well understood, and side eects

of nervousness, appetite suppression and in-

somnia are common. In addition, non-thera-

peutic high-dose use can lead to addiction.

The researchers also warn that the medica-

tion may aect a developing patients sense of

authenticity. While neuroenhancements may

help some develop a more authentic sense of

self, others may nd that these medications

alter their personality and constrain their

sense of self. This is of particular importance

at a time when children and adolescents are

still developing their personality.Graf and colleagues warned that if social

acceptance of neuroenhancement continues,

this type of medication could become the new

normal. Children and adolescents may face

added pressure to take neuroenhancement

medication in order to keep up with or stay

ahead of their peers.

They also emphasized that it is the job of

the doctor to protect their patients from these

dangers. The decision to treat a patient with

neuroenhancement should be made between

the doctor, parent and patient with particular

aention paid to any medical, social or psy-

chological motivations.

Graf noted that good sleep, nutrition, study

habits and exercise regimens may be good al-

ternatives to neuroenhancements.

CJD may cause rapid hearing loss

Saras Ramiya

Patients presenting with rapid hear-

ing loss in both ears should be testedfor Creutzfeldt-Jakob disease (CJD), US re-

searchers say.

That was the conclusion of Henry Ford

Hospital researchers aer encountering a

67-year-old patient who had been progres-

sively losing hearing in both ears for 2 months

and was eventually diagnosed with the

disease.

The researchers ndings were only the

fourth time, based on available literature,

that hearing loss such as that found in their

patient was recognized as the rst symptom

of CJD.

US researchers have suggested that patients presenting with hearing lossshould be tested for CJD.


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12 April 2013 News

The report was presented during the

annual scientic meeting of the American

Academy of Neurology in San Diego in

March.

When the patient sought treatment, hecomplained only of a continuing, rapid loss

of hearing in both ears, and tinnitus. This

was followed by cognitive decline that is

typical of CJD.

Testing found the presence of a telltale

protein and other conditions that led to a

diagnosis of CJD. The researchers noted that

the patients hearing never improved and he

died a month aer seeking treatment.

CJD is always fatal and other symptomsinclude impaired thinking, jerky body move-

ments, memory loss and dementia. Once

infected with CJD, the brain develops holes,

resulting in tissue which resembles a

sponge.

Link between HRT and breast cancerdisputed

Laura Dobberstein

Contrary to past reports, a new study saysthere is no denitive evidence linking areduction in hormone replacement therapy(HRT) use to a decline in new cases of breast

cancer.

We concluded that HRT may or may not

cause breast cancer, but the studies did not

establish that it does, wrote the study au-

thors, led by Dr. Samuel Shapiro of the Uni-

versity of Cape Town in South Africa. [J Fam

Plann Reprod Health Care2013;39:80-88]

Claims linking HRT use with breast can-cer, made based on the ndings of three re-

ports the Collaborative Reanalysis (CR),

the Womens Health Initiative (WHI), and

the Million Women Study (MWS) have

been aributed with a fall in HRT prescrip-

tions in many countries.

Shapiro and colleagues reexamined these

three reports, looking for possible con-

founding factors which may have otherwise

explained the association.

What they found was that breast cancer

rates began declining in 1999, 3 years be-fore studies linking HRT and breast cancer

were released in 2002. Because it takes years

for breast cancer tumors to develop, the re-

searchers concluded that any fall in breast

cancer rates due to reduction in HRT use

would have taken place over a longer time

frame.

The rates at which the cancer statistics

dropped were also questioned by the re-

searchers. They suggested that a reported 11

Women who have stopped using HRT may be abandoning a potentiallyhelpful treatment.


13/32

13 April 2013 News

percent reduction in new breast cancer cases

in 2003 was too aggressive a change to be

seen over a 1-year period.

Data in one study from the US National

Cancer Institutes Surveillance, Epidemiol-

ogy and End Results (SEER) had drops in

early cancer that were similar to those seen

in advanced breast cancer. The researchers

called such a reduction in advanced cancers

unlikely as advanced cancer takes longer

to develop than early cancer and would

have shrunk too rapidly after discontinu-

ing HRT.

The study authors suggested a study

group that does not accurately reect the

population or other inuential factors may

have caused the appearance of a link.

In an accompanying editorial, Dr. Nick

Panay, chairman of the British Menopause

Society and consultant gynecologist at Queen

Charloes & Chelsea Hospital, London, UK,also suggested that changes in HRT since the

publication of WHI may completely change

any risk associated with the treatment. HRT

is now prescribed in lower doses, admin-

istered in dierent methods and made of a

dierent combination of hormones. [J Fam

Plann Reprod Health Care2013;39:72-74]

Many women that have eliminated the use

of HRT could be abandoning a potentially

helpful treatment owing to unsubstantiated

claims, said Panay.

If there is a risk, the risk is small, and the

benets of HRT can be life-altering; it is vital

that we keep this in perspective when coun-

seling our patients, he said.

If there is a risk,

the risk is small


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14 April 2013 Conference Coverage6th ASEAN Rehabilitation Medicine Association Congress, February 21-23, Manila, Philippines

Dry needle technique relieves chronic

upper back pain

Dr. Carol Tan

The dry needle technique is an eec-tive treatment modality for alleviatingchronic upper back pain, new research

has shown.This technique involves the insertion of

solid liform needles into myofascial triggerpoints, which are composed of multiple con-traction knots that produce pain. This tech-nique is hypothesized to relieve pain by acti-vating endogenous opioids.

In a study conducted by researchers fromthe University of Health Sciences Depart-ment of Rehabilitation Medicine in Laos, the

dry needle technique was found to be moreeective than the use of non-steroidal anti-in-ammatory drugs (NSAIDs) in relieving painamong patients with chronic upper back pain.

The study involved 400 adult patients whoconsulted at Setharthirath Hospital from Janu-ary to December 2007 and were diagnosed withchronic myofascial pain syndrome. The pa-tients age ranged from 30 to 50 years old, with

an average age of 41 years. There were 200 maleand 200 female patients; half of each sex groupwere farmers and the other half were ocers.

The patients were separated equally into twogroups based on sex and occupation. One groupwas given NSAIDs 7.5 mg once a day and mus-cle relaxants 500 mg thrice a day. The dry needletechnique was applied in the other group. Thepatients were treated for seven days, and theirpain levels were assessed daily.

In the group treated with dry needle tech-nique, 68 percent of the patients achieved

pain relief on the first day. The remaining32 percent achieved pain relief on the sec-ond day. The patients did not report any

adverse side effects. In contrast, among thepatients treated with NSAIDs and musclerelaxants, 52 percent reported pain reliefon the second day of treatment, 37 percenton the third day, and the remaining 11 per-cent on the fourth day. In addition, amongthe patients who reported pain relief on thefourth day, 89 percent complained of dizzi-ness and 67 percent complained of fatigue.

The authors concluded that dry needletechnique is an excellent treatment modal-ity for patients with chronic upper backpain caused by myofascial pain syndrome.They found that this technique not only al-leviates pain more quickly than NSAID use,

but it also has no side effects and is muchcheaper. However, it has not been provento be effective for other causes of chronicupper back pain, such as disc herniation,

osteoarthritis, spondylosis, spondylitis,fractures and bone neoplasms.

This technique is hypothesized to relieve pain by activating endogenousopioids.


15/32

15 April 2013 Conference Coverage

Robot-assisted rehab may be superior to

usual therapy

Dr. Nicolo Cabrera

Apilot systematic review of 33 articles onrobot-assisted neuromotor rehabilita-tion for upper limbs and 30 for lower limbsshowed a trend toward superior functionalrecovery compared to usual therapybutwas not statistically signicant.

Investigators searched the electronic da-tabases of MEDLINE via PubMed, Embaseand Google Scholar for controlled trials witharticle in English from 2001 through 2010.Short- and long-term motor control as well asmotor strength was improved. Some cases ofreduction in spasticity were found, but painwas unchanged.

The experimental intervention had no con-sistent impact on the performance of func-

tional tasks such as activities of daily living(ADL) in multiple sclerosis, cerebral palsy orspinal cord injury.

With respect to the upper limb, results var-ied according to the greater intensity of thetreatment as measured by the higher number ofrepetitions of task-specic exercises. In strokepatients, bilateral therapy resulted in beer mo-tor recovery than unilateral therapy. In patients

undergoing therapy for lower limbs, achieve-ment of the siing position in the wheelchairduring the early phase and achievement of thestanding position later were seen.

Biofeedback, the use of instrumentation tomake covert physiological processes overt,may be clinically applied to improve a pa-tients motor control through re-educatingthat control using visual or audio feedbackwith the help of electromyelogram, positionaland force parameters in real time.

Precise mechanisms are unclear, but

previous review of studies suggested thatnew pathways may develop or an auxiliaryloop recruits existing pathways that are un-used or underused in the execution of mo-tor commands. [J Neuroeng Rehabil 2006;

doi:10.1186/1743-0003-3-11]Continued training could then later

establish new sensory engrams that wouldallow the patient to later engage in improvedmotor activity without feedback, according tothe review. One of the current developmentsin the area of biofeedback for neurorehabili-tation is a shi from static to task-orientedfeedback, which may have an advantage in

improving functional ADL tasks.In the same review on biofeedback thera-

py, its limitation was recognized in patientswith severe motor decits, with patients un-able to initiate any functional movementat all, leaving them with no biofeedbackto capitalize on. Rehabilitation robots ad-dress this issue by providing mechanicalassistance for movement. The review awaitednew studies that will pursue the combinationof robotics and advanced biofeedback as anapproach for sensorimotor rehabilitation.


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Interview with new ESC President

Asian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand

The European Society of Cardiology (ESC) was well represented at the recent

Asian Pacic Society of Cardiology (APSC) Congress and even hosted its

own stream of lectures in the scientic program, under the theme of ESC in

Asia Pacic. The new ESC president, Professor Panagiotis Vardas (PV), was

in aendance and Medical Tribune(MT) had the opportunity to interview

him.Monika Stiehl reports.

MT: What were the main tasks of the ESC at

the APSC Congress?

PV: We are here supporting the huge strategic

project named Global Scientic Activities. This

project includes countries which are not regu-

lar members of ESC like China, India, Saudi

Arabia, Brazil and Argentina, to name a few.

And in this context we are visiting some bigger

congresses, like the APSC, and of course par-ticipating in the scientic program. The gen-

eral part of ESC here at the APSC was to give

a summary and ve take-home messages from

the ESC Congress last year in Munich.

MT: What in your opinion were the most im-

portant topics here at the APSC Congress?

PV: Here ... we had a number of important

issues to discuss related to cardiovascularmedicine. In my opinion, in invasive cardiol-

ogy, [for example, one of the issues is] trans-

catheter aortic valve implantation, which

means repairing aortic valves through the ar-

teries without operation. Our experience in

this technique is geing beer and the eec-

tiveness of this therapy is proven. [We also

discussed] mitral clips and the eld of mitral

valve repair also without any operation. This

is a hot and evolving new topic in cardiovas-

cular medicine.

MT: At the end of August this year we will

have the ESC Congress in Amsterdam. What

can we expect?

PV:[The ESC Congress in] Amsterdam is ex-

pected to be a huge success. We have the rst

indications about the size of the congress. It

was really a pleasant surprise for us, to see thatin spite of the economic crisis in Europe the

number of abstract submissions was a new re-

cord. It is much higher than in Munich last year

about 10,500 abstracts. This is a strong indica-

tion that the number of delegates will be large

as well. And the [number of] satellite symposia

is expected to be more than in Munich. We are

going to organize a great event in Amsterdam

with around 27,000 to 30,000 participants.

MT: Can we expect some changes in the ESC

guidelines this year?

PV: Yes, in Amsterdam we are going to

announce a number of new guidelines. We

expect new guidelines for example in pacing

and in arterial hypertension, to name two of

them. We have to see how many of them are

ready but at least three or four new guidelines

will be announced.

ProfessorPanagiotis Vardas

ESC president


17/32


Elvira Manzano

Much has been learned about heart fail-ure with preserved ejection fraction(HF-PEF), but there remains no clear pharma-

cologic treatment for this syndrome.

HF-PEF may be as common and as inca-

pacitating as heart failure with reduced ejec-

tion fraction (HF-REF), however the value of

pharmacologic therapy in HF-PEF is uncer-

tain, said Dr. Karl Swedberg from the Sahl-

grenska Academy, University of Gothenburg

in Gothenburg, Sweden. Diuretics may be

used to control sodium and water retention

angiotensin-converting enzyme (ACE) inhibi-

tor or angiotensin receptor blockers (ARBs)

and a beta-blocker seem reasonable, but no

treatment has been shown convincingly yet to

reduce morbidity and mortality in patients.

In the ALLHAT* study involving hyperten-

sive patients, risk of new-onset HF was higher

in the amlodipine and lisinopril arms com-

pared with the chlorthalidone arm. Aer a di-

agnosis of HF, the subsequent 5-year mortalityrate was similar between subjects with HF-

PEF and HF-REF. [Circulation 2008;118:2259-

2267] Current ESC guidelines for HF-PEF

therapy focus on optimizing blood pressure

control, use of lowest dose diuretics to con-

trol uid overload, control of HR extremes

(chronotropic failure or rapid atrial brilla-

tion), managing comorbidities, weight loss

and exercise training. However, the guide-lines do not provide information on how to

specically achieve these goals. Many studies

looking at the eect of ACEIs/ARBs and beta-

blockers on HF hospitalization or CV death

(the PEP-CHF, the CHARM-preserved trial,

I-PRESERVE) have been conducted with con-

icting results.

In practice, most patients receive an RAAS

inhibitor. Clinical trials however have failed to

show any signicant benet of RAAS block-

ade in the prevention or treatment of HF-PEF.

The use of RAAS inhibitors was associ-

ated with lower all-cause mortality in a large

national registry involving 41,791 patients in

the Swedish Heart Failure Registry. However,

the study included patients with ejection frac-

tions (EFs) of >40 percent. The results were

non-signicant when the study was limited

to patients with EFs of >50 percent. [JAMA

2012;308:2108-2117]

Although inhibitors of the RAAS and sym-

pathetic nervous system should continue to

be used in patients with HF-PEF who have

comorbidities (hypertension, diabetes or cor-

onary artery disease), the use of these drugsfor the primary treatment of HF-PEF remains

unsupported by the available evidence.

Treatment of HF-PEF remains empirical

and centered around blood pressure control

and volume control. Clearly, new therapies

should improve quality of life and increase

mortality benet, said Swedberg.

*ALLHAT: Antihypertensive and Lipid-Lowering Treatment to Prevent

Heart Aack Trial

Novel therapies, more research needed

in HF-PEF



18/32


Personal Perspectives

It is indeed a very interesting experience for us cardiologists fromthe Philippines. Especially the sessions and discussions about heart

failure patients and coronary artery disease [these] were very

informative as well as the summary of the European Society of

Cardiology of their recommendations. That will be very helpful for

our patients back home.

Dr. Diana Jean Roxas, cardiologist, St. Lukes Medical Center, Quezon

City, Philippines

It was very interesting for me to be at the APSC. One of the main

important topics for me was hypertension. I have learnt a lot about

new drugs and treatments against high blood pressure and in our

country hypertension is currently a very serious problem.

Dr. Evy Febriane, cardiologist, Royal Hospital Surabaya, Surabaya,

Indonesia

I was very impressed by the enthusiasm of the Asian Pacic

[Cardiology] Society to set up such a huge congress here in theregion. And what especially is notable, that the Asian Pacic countries

collaborate so well to organize international congresses in the area

which I believe is very important especially when you look at the

prevention eorts that need to be made in this area.

Professor Stefan Gielen, deputy director of cardiology,

University Halle-Wienberg, Halle, Germany

I am quite satised with the results of the APSC congress... We have

about 1,600 delegates from 60 countries around the world.

[Going forward the APSC plans to expand its network.] Right now

we have 18 countries as a member, but we have a lot more countries

in the Asian Pacic region which could join the society. We should try

to expand and work more together. It is important that we share our

knowledge in terms of new techniques in cardiology, complications of

treatments or side eects in new drugs.

General Dr. Prasart Laothavorn, Heart Association of Thailand,

APSC 2013 Congress chairman


19/32

19 April 2013 Conference CoverageAsian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand

Asian CV, diabetes risk profile unique

Elvira Manzano

The rising tide of cardiovascular diseasein Asia includes patients who do not al-ways t into standard Western calcula-

tions for high cardiovascular or diabetes risk,but who should nevertheless be targeted forsurveillance and preventive measures, says

one expert.They represent a unique prole of skinny

diabetics who are not obese but have higherblood glucose levels than their Western coun-terparts, said Associate Professor CarolynLam, consultant, National University HeartCentre, Singapore.

Asian women have greater central adipos-ity (higher waist-to-hip ratio, higher truncalfat and visceral fat) than Caucasian women,which may explain their greater metabolicrisk, Lam said. This suggests that Asians neednot weigh >100kg to become diabetics.

Clinicians should also recognize that thele ventricular mass index (LVMI) cutos rec-ommended by the American Society of Echo-cardiography for the diagnosis of le ven-tricular hypertrophy (LVH) may need to belowered in Asians as research has shown that

Asian patients, particularly Chinese, Malaysand Indians, have consistently lower LVMIvalues than Western patients.

If we are to use cutos derived fromWestern populations, there is a potential tounderdiagnose LVH and under-recognize thetransition of stage A to stage B HF, Lam said.Ethnicity-specic cutos should then be usedto assess for structural changes (le ventricu-

lar remodeling and dysfunction) which arestrongly associated with heart failure (HF).She also highlighted that stage C or overt

congestive HF, characterized by increasedbreathlessness, fatigue and uid retention,occurs at a younger age in Asian patients andis associated with a high prevalence of diabe-tes despite relative lack of obesity comparedwith Western cohorts.

Important inter-ethnic dierences mayexist which may aect management. Endo-thelial dysfunction, which is linked to renaldysfunction, is also highly prevalent amongAsian patients with HF. It therefore representsa particularly aractive therapeutic target.

When it comes to medical therapy, use ofdisease-modifying HF agents (beta-blockers,ACE inhibitors, ARBs, vitamin K antagonists)was also lower in the Asia Pacic region com-

pared with the US and Europe, which repre-sents a potential opportunity for improvingtreatment outcomes, she said. Device therapyis also underused and poorly accepted.

Lam is optimistic that three ongoing stud-ies, the Singapore Heart Failure Outcomesand Phenotypes (SHOP), the Asian SuddenCardiac Death in HF (ASIAN-HF) and theOutcome in Patients with Heart Failure with

a Preserved Le Ventricular Ejection Fraction(PEOPLE) study, will ll the knowledge gapsin HF in Asia.

Asian patients dont necessarily t Western models of high CV or diabetes risk.


20/32


GRACE score underestimates ACS

mortality risk in Asians

Monika Stiehl

The commonly used Global Registry ofAcute Coronary Events (GRACE) under-estimates in-hospital mortality risk score for

Asian patients with acute coronary syndrome

(ACS), according to the results of a Singapore

study.

You cant say that one [score] ts all, said

lead study author Assistant Professor Mark

Y. Chan from the National University Heart

Centre, Singapore. We have to be specic

and sensitive to dierences in both ethnicity

as well geographical location, when we are

performing risk stratication for acute coro-

nary syndrome.

In the study, Chan and colleagues evaluat-

ed the performance of GRACE in a large Sin-

gaporean cohort which included 10,100 Chi-

nese, 3,005 Malay, and 2,046 Indian patients

hospitalized in Singapores public healthcare

system for acute myocardial infarction from

2002 to 2005. [Am Heart J2011;162:291-299]

The GRACE mortality risk model was ini-tially calibrated based on data from 11,389

patients with acute myocardial infarction or

unstable angina admied to hospitals around

the world from 2002 to 2003. These patients

were predominantly of European descent;

no Asian patients were included. The model

takes into account eight major patient risk

factors age, serum creatinine levels, systolic

blood pressure, heart rate, initial cardiac en-

zyme elevations, heart failure severity, ST el-

evation or depression 1mm, and cardiac ar-

rest at presentation.

The Singapore researchers reported that,

in reality, in-hospital mortality rates in the

three dierent ethnicities tested were much

higher than the rates predicted using the

GRACE score. According to the GRACE

score, predicted in-hospital mortality rates

were 2.4 percent for Chinese, 2.0 percent for

Malays, and 1.6 percent for Indians. How-

ever, the corresponding actual observed in-

hospital mortality rates were 9.8 percent, 7.6

percent and 6.4 percent, respectively.

External risk scores for coronary heart

disease should be tested and recalibrated in

all unique, previously untested populations

before used, said Chan.

Using a recalibrated GRACE score, taking

into account risk factors for Singaporeans,

the researchers showed a lower mismatch,

but there was still an underestimation of risk.Good accurate risk stratication facili-

tates appropriate healthcare allocation and is

associated with beer outcomes, concluded

Chan, adding that more Pan-Asian risk-

stratication studies are needed to adapt

externally developed risk scores for Asian

populations.



21/32


New pacemaker device safe during MRI

Alexandra Kirsten

Arecent study has shown that a new du-al-chamber pacemaker system calledEnRhythm MRI SureScan Pacing System

(Medtronic) is safe for patients undergoing

magnetic resonance imaging (MRI).

MR scanning in patients with conven-tional pacemakers is possible, but it is a rela-

tive contraindication since the risk can only

be limited but not excluded, said study au-

thor Professor Torsten Sommer, director of

the Department of Diagnostic and Interven-

tional Radiology and Nuclear Medicine in

Neuwied, Germany.

In the trial 258 patients with arrhythmias

were randomized to undergo MRI 9 to 12weeks aer successful implantation of the

device. They were compared with a control

group who received the same pacemaker sys-

tem but did not undergo MRI (n=206).

The patients were monitored for arrhyth-

mias, symptoms and pacemaker system func-

tion during 14 nonclinically indicated rel-

evant brain and lumbar MRI sequences. The

pacemaker system function was checked im-mediately before and aer MRI, 1 week and 1

month post-MRI, and at corresponding times

for the control group. [Heart 2011;8:65-73]

The study showed that no MRI-related com-

plications occurred during or aer the MRI

scans. This included sustained ventricular

arrhythmias, pacemaker inhibition or output

failures, electrical resets, or other pacemaker

malfunctions. Pacing capture threshold and

sensed electrogram amplitude changes were

minimal and similar between study groups.Performing an MRI in patients with a con-

ventional pacemaker is limited to those with

urgent clinical need and requires dedicated

precautionary measures consuming man-

power and MRI system time, said Sommer.

Nevertheless, it still remains an o-label use

with potential medico-legal consequences.

Given that MRI is the gold standard for im-

aging of the brain and spinal cord, and is veryimportant for scanning the liver, breast and

musculoskeletal system, a wider use of MRI-

safe pacemaker devices should be considered.

According to Sommer there are no medical

reasons only cost-benet assessments to

deny a patient an MRI-compatible pacemaker.

If indications for MRI-conditional pace-

maker systems are not expanded to all pa-

tients, the devices should be used at least inthose who have undergone prior scans [and

who will likely receive future MRI], and in

those with long life expectancy.



22/32


Radha Chitale

Some doctors still fail to prescribe life-sav-ing beta-blockers to heart patients in fa-vor of symptom-relieving drugs, especiallyamong the elderly, said Dr. Michel Komajda,a cardiologist at the Piti Salptrire Hospi-tal in Paris, France, and former president ofthe European Society of Cardiology (ESC).

The trend against providing beta-block-ers, which reduce the stimulating eects ofstress on cardiac and other tissues, and re-duce the risk of secondary heart aack andhypertension, was identied in a surveyfrom the ESCs EURObservational ResearchProgramme. [Eur J Heart Fail 2010;12:1076-

1084]There are some good reasons [to not

prescribe beta-blockers] but in some otherinstances, it is simply the reluctance of pre-scribers to provide life-saving drugs and wetherefore need to continue to provide educa-tion programs, Komajda said.

According to the survey, the rate of beta-blocker prescription was 86.7 percent.

However, Komajda pointed out that theproportion of patients enrolled in this regis-try is about 40 percent at best.

The situation is even worse when youlook at the proportion of patients who reachthe target dose of beta-blockers, he said.

The survey showed that less than 40 per-cent of patients reached target dosing for

beta-blockers.

Prescribing beta-blockers or other renin-angiotensin-aldosterone system (RAAS) in-hibitors can be problematic in elderly people.Most of these drugs are cleared through thekidneys, which can become dysfunctionalwith age. Consequently, the half-life of thesedrugs in the body can double or triple.

For the elderly, prescribing symptom-relieving drugs may be becoming a trend,Komajda said, which is unfortunate becausethe Euro Heart Failure Survey showed thatin-hospital mortality was signicantly inu-enced by patients not receiving beta-block-ers and other RAAS blockers. [Eur Heart J2007;28:1310-1318]

Age is not a good reason not to provide

life-saving drugs to these patients, Koma-jda said.

Consistent education about the use of be-ta-blockers pays dividends.

In three surveys of about 2,000 patientseach, given aer an updated version of theESC guidelines for heart failure were re-leased, beginning in 2004, the rate of pre-scriptions for beta-blockers increased (from

65 to 78 percent) and so did the proportion ofpatients who reached the target dose (18 to 26percent), or at least half of the target dose (47to 60 percent). [Eur J Heart Fail2009;11:85-91]

Komajda noted this trend had positive im-pacts on overall patient survival as, over thelast 15 years, Europe has seen a signicantdecline of hospitalization and of mortalityamong heart failure patients.

Beta-blocker prescription practices need

improvement



23/32

23 April 2013 Research Reviews

Tolvaptan for autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive kidney cysts, renal pain, hy-

pertension and renal failure, and is the fourth most common cause of end-stage kidney disease in adults.Animal studies have suggested that vasopressin promotes cyst expansion. Preliminary trials suggest that tolvap-

tan, a vasopressin V2-receptor antagonist, might be benecial in ADPKD. Now, a large international trial has

conrmed its benets.

At 129 centers worldwide, a total of 1,445 patients aged 18-50 years with ADPKD were randomized (2:1) to

tolvaptan or placebo. The increase in kidney volume over a period of 3 years was 2.8 percent per year (tolvaptan)

vs 5.5 percent per year (placebo), a signicant dierence, and the decline in kidney function was signicantly

slower with tolvaptan. The rate of discontinuation of treatment was 23 percent vs 14 percent. The increased rate

of discontinuation with tolvaptan was largely due to increased aquaresis (excretion of electrolyte-free water) and

hepatic adverse events.

Tolvaptan slowed the increase in kidney volume and the decline in renal function in patients with

ADPKD but was associated with a high rate of discontinuation because of adverse events.

Torres VE et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. NEJM 2012;367:2407-2418; Wthrich RP, Mei C. Aquaretic

treatment in polycystic kidney disease. Ibid: 2440-2442 (editorial).

Cinacalcet for chronic dialysis patients: Negative trial

Patients receiving hemodialysis for chronic kidney disease have a risk of death from cardiovascular diseaseat least 10 times that of the general population. One of many factors possibly contributing to this risk is sec-ondary hyperparathyroidism with intra-arterial calcication. Cinacalcet lowers levels of parathyroid hormone,

calcium and phosphorus by activating the parathyroid calcium-sensing receptor. Previous trials have reported

a reduction in cardiovascular risk aer treatment with cinacalcet. Now a large, multinational trial has shown no

reduction in cardiovascular risk with use of cinacalcet in dialysis patients with secondary hyperparathyroidism.

A total of 3,883 dialysis patients with moderate-to-severe secondary hyperparathyroidism were randomized

at centers in North America, Europe, Latin America and Australia to cinacalcet 30 mg daily (increased as neces-

sary to a maximum of 180 mg daily) or placebo, and followed for up to 64 months. The median duration of study

drug administration was 21.2 months (cinacalcet) vs 17.5 months (placebo). The primary composite endpoint

(death, myocardial infarction, hospital admission for unstable angina, heart failure or peripheral vascular event)

was reached by 48.2 percent (cinacalcet) vs 49.2 percent (placebo), a nonsignicant dierence. Hypocalcemia and

gastrointestinal problems were more frequent in the cinacalcet group.

Cinacalcet was not eective in reducing cardiovascular risk in this trial. Editorialists point to problems with the

trial including the fact that almost two-thirds of patients in the cinacalcet group discontinued treatment and one-

h of patients in the placebo group began to take commercially available cinacalcet, thus considerably reducing

the power of the trial. Adjusted analyses suggested a possible reduction in cardiovascular risk with cinacalcet.

The EVOLVE trial investigators. Eect of cinacalcet on cardiovascular disease in patients undergoing dialysis. NEJM 2012;367:2482-2494; Perkovic V,

Neal B. Trials in kidney disease time to EVOLVE. Ibid:2541-2542 (editorial).


24/32


ICP monitoring in brain trauma: Not effective

I

ntracranial pressure (ICP) monitoring has been wide-

ly used in the management of severe traumatic brain

injury but evidence of its eectiveness is lacking. Now

a multicenter study in Bolivia and Ecuador has shown

similar outcomes with or without ICP monitoring.

At four hospitals in Bolivia and two in Ecuador a total

of 324 patients aged 13 years or older with severe trau-

matic brain injury and in intensive care were random-

ized to care with (target ICP


25/32


Cinacalcet for chronic dialysis patients: Negative trial

Patients receiving hemodialysis for chronic kidney disease have a risk of death from cardiovascular disease

at least 10 times that of the general population. One of many factors possibly contributing to this risk is sec-ondary hyperparathyroidism with intraarterial calcication. Cinacalcet lowers levels of parathyroid hormone,

calcium and phosphorus by activating the parathyroid calcium-sensing receptor. Previous trials have reported

a reduction in cardiovascular risk aer treatment with cinacalcet. Now a large, multinational trial has shown no

reduction in cardiovascular risk with use of cinacalcet in dialysis patients with secondary hyperparathyroidism.

A total of 3,883 dialysis patients with moderate-to-severe secondary hyperparathyroidism were randomized at

centers in North America, Europe, Latin America and Australia to cinacalcet 30 mg daily (increased as necessary

to a maximum of 180 mg daily) or placebo, and followed for up to 64 months. The median duration of study

drug administration was 21.2 months (cinacalcet) vs 17.5 months (placebo). The primary composite endpoint

(death, myocardial infarction, hospital admission for unstable angina, heart failure or peripheral vascular event)was reached by 48.2 percent (cinacalcet) vs 49.2 percent (placebo), a nonsignicant dierence. Hypocalcemia and

gastrointestinal problems were more frequent in the cinacalcet group.

Cinacalcet was not eective in reducing cardiovascular risk in this trial. Editorialists point to problems with the

trial including the fact that almost two-thirds of patients in the cinacalcet group discontinued treatment and one-

h of patients in the placebo group began to take commercially available cinacalcet, thus considerably reducing

the power of the trial. Adjusted analyses suggested a possible reduction in cardiovascular risk with cinacalcet.

The EVOLVE trial investigators. Eect of cinacalcet on cardiovascular disease in patients undergoing dialysis. NEJM 2012;367:2482-2494; Perkovic V,

Neal B. Trials in kidney disease time to EVOLVE. Ibid:2541-2542 (editorial).

Management of polycythemia vera

The optimum management of polycythemia vera is debated. Commonly the aim is to maintain a hematocritvalue of


26/32


Pandemic flu vaccine and epileptic seizures: No link

V

accination against the 2009 pandemic A/H1N1 inuenza

virus has been associated with increased risk of neurologi-

cal disorders such as Guillain-Barr syndrome and narcolepsy.

A study in Sweden has shown no increase in epileptic seizures

among people with or without epilepsy aer receiving the vac-

cine.

The study included 373,398 people of all ages (median age 41.2

years) in three Swedish counties who were given the monovalent

AS03 adjuvanted pandemic A/H1N1 inuenza vaccine. Epileptic

seizures were recorded in 859 individuals during the period from 90 days before to 90 days aer vaccination.

Among people with prior epilepsy there was no increase in risk of epileptic seizures during the periods from 1-7

or 8-30 days aer receiving the vaccine. Among people without a prior diagnosis of epilepsy there was a nonsig-

nicant decrease in risk at 1-7 days post-vaccination and a nonsignicant increase at 8-30 days.

The pandemic inuenza vaccine did not aect the risk of epileptic seizures aer vaccination in people with or

without prior epilepsy.

Arnheim-Dahlstrm L et al. Risk of presentation to hospital with epileptic seizures aer vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009

inuenza vaccine (Pandemrix): self controlled case series study. BMJ 2013;346 (Jan 5) 11 (2012; 345: e7594).

Serelaxin for heart failure

There have been no new eective treatments for acute heart failure in recent years. Serelaxin is recombinanthuman relaxin-2, a naturally occurring peptide active in pregnancy with cardiovascular eects includingincreased arterial compliance, cardiac output and renal blood ow. It has been assessed for the treatment of

acute heart failure in an international trial.

A total of 1,161 patients (mean age 72 years, 62 percent men) admied to hospital with acute heart failure at

96 sites in 11 countries were randomized within 16 hours of presentation to serelaxin 30 g/kg/day or placebo, by

IV infusion for 48 hours, in addition to standard care. Serelaxin signicantly improved dyspnea over the rst

5 days as measured by the visual analogue scale area under the curve, but not the proportion of patients with

moderate or marked improvement in dyspnea in the rst 24 hours (Likert scale). There were no signicant group

dierences in rates of cardiovascular death, hospital readmission for heart failure, renal failure, or survival out

of hospital up to day 60. Mortality by day 180 was signicantly less in the serelaxin group (7.2 percent vs 11.2

percent, respectively). The drug was well tolerated.

Serelaxin relieved dyspnea in patients with acute heart failure and reduced 180-day mortality. A Lancet com-

mentator raises several caveats but in general seems optimistic about the new drug.

Teerlink JR et al. Serelaxin, recombinant human relaxin-2, for the treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet

2013; 381:29-39; Konstam KA. RELAX-AHF: rising from the doldrums in acute heart failure. Ibid: 5-6 (comment).


27/32


Z drugs for insomnia

T

he Z drugs (non-benzodiazepine hypnotics includ-

ing eszopiclone, zaleplon and zolpidem) are now

the most commonly prescribed hypnotics worldwide,

with prescription costs in the UK alone amounting to

over 25 million per year. Now a meta-analysis of data

submied to the US Food and Drug Administration has

shown that these drugs are superior to placebo in the

treatment of insomnia.

The meta-analysis included 13 studies with 65 sepa-

rate drug-placebo comparisons and a total of 4,378 par-

ticipants. Z drugs were signicantly beer than placebo

in improving both subjective and polysomnographic

sleep latency. They reduced polysomnographic sleep

latency by an average of 22 minutes compared with pla-

cebo. Factors associated with reduction of sleep latency

with Z drugs were larger doses, younger age, female

sex, and use of zolpidem. There were too few studies re-

porting other outcomes, such as waking aer sleep on-

set, number of awakenings, total sleep time, and sleep

eciency or quality, for valid conclusions to be made

about the eects of Z drugs on these outcomes. On combining the eects of drug and placebo the reduction in

sleep latency with drug treatment increased to 42 minutes.

Z drugs reduce sleep latency. The authors of this meta-analysis conclude that, although Z drugs and placebo

separately produce only small and probably clinically insignicant eects, the two eects together produce a

reasonably large eect. An editorialist concludes that it is misguided to rely on hypnotics alone to treat insomnia

and other treatments such as cognitive and behavioral therapy for insomnia (CBTi) should be considered.

Huedo-Medina TB et al. Eectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submied to the Food and

Drug Administration. BMJ 2013;346:10 (2012; 345: e8343); Cunnington D. Non-benzodiazepine hypnotics: do they work for insomnia? Ibid: 8 (2012;

345: e8699) (editorial).


28/32


Discrimination against people with depression

Around the world, stigma and discrimination against people

with depression are common. A study in 35 countries on sixcontinents has illustrated the worldwide scale of this discrimination.

People with a major depressive disorder were interviewed at 39

sites in the 35 countries and 1,082 people completed the discrimi-

nation and stigma scale, version 12 (DISC-12). Discrimination in at

least one life domain was reported by 885 participants (79 percent).

Many participants (37 percent) had refused to initiate a close per-

sonal relationship, 25 percent had backed o applying for a job, and

20 percent had stopped themselves applying for education or training. Experience of discrimination was posi-

tively associated with lifetime recurrence of depressive episodes, admission to psychiatric care, poorer socialfunctioning, unpaid employment, job seeking, and unemployment. Experience of discrimination also increased

the likelihood of concealing depression. Anticipated discrimination was common but almost half (47 percent)

of people who anticipated discrimination in employment or relationships had not experienced discrimination.

Discrimination against people with depression is common and interferes with social participation and em-

ployment prospects. Non-disclosure of depression is a further negative feature. New approaches to prevent the

stigmatization of people with depression are needed.

Lasalvia A et al. Global paern of experienced and anticipated discrimination reported by people with major depressive disorder: a cross-sectional survey.

Lancet 2013;381:55-62; Jorm AF, Reavley NJ. Depression and stigma: from aitudes to discrimination. Ibid: 10-11 (comment).

Falls in the elderly: Video study

Researchers in Canada have used digital video cameras tostudy falls in two long-term care facilities for the elderly.A total of 227 falls (130 individuals, mean age 78 years) were

captured on video. The most frequent causes were incorrect

weight shiing (41 percent of falls), trip or stumble (21 percent),hit or bump (11 percent), loss of support (11 percent), collapse

(11 percent), and slipping (3 percent). Falls commonly occurred

during forward walking (24 percent). Compared with previous

studies, this one has shown a higher proportion of falls during

standing and transfering, more due to changes in center of grav-

ity than in alterations of support base, and fewer during walking.

It is hoped that these observations will promote advances in risk assessment and fall prevention.

Robinovitch SN et al. Video capture of the circumstances of falls in elderly people residing in long-term care: an observational study. Lancet 2013;383:47-

54; Becker C, Chiari L. What videos can tell us about falling. Ibid: 8-9 (comment).


29/32

29 April 2013 Congress Spotlight

World Congress of Thoracic Imaging in

Seoul, Korea

Monika Stiehl

The 3rd World Congress of Thoracic Im-aging (WCTI), which is held every 4years, will take place in Seoul, South Ko-

rea this year from June 8-11. An estimated 1,600participants from about 50 countries, includ-ing chest radiologists and other health profes-

sionals involved in thoracic imaging, will sharetheir knowledge in chest diseases and discussnew scientic ndings and advances in imag-ing techniques. There will also be presentationsof guidelines and recommendations for appro-priate practice in chest imaging. As of March16, a total of 509 abstracts on a wide range ofrelevant topics had been submied from 33countries.

A large number of professors, doctors anddistinguished leaders from all around the worldas well as ve member societies are coming to-gether to discuss recently emerging issues and

exchange the latest information in the eld ofthoracic radiology, announced Dr. Jun-Gi Im,president of the WCTI Organizing Commiee.

The WCTI 2013 scientic program will covertopics such as lung cancer screening, pulmo-nary embolism and drug-induced lung dis-eases. Possibilities in radiation dose reduction,especially in pediatric thoracic imaging, will bediscussed, as well as the elds of chronic ob-structive pulmonary diseases (COPD), asthma,infection, and coronary and cardiovasculardiseases.

Another important focus of the congress willbe digital tomosynthesis, which is a simple andrelatively inexpensive method of producingsection images of the chest and the breast us-ing conventional digital X-ray equipment. To-mosynthesis is able to make three-dimensionalpictures and has some potential to improve the

diagnosis of breast cancer and pulmonary nod-ules.

New developments in interventional radiol-ogy, positron emission tomography (PET), X-ray computed tomography (CT) and magneticresonance imaging (MRI) will top up the con-gress.

The organizing commiee is planning toprovide an opportunity to dig deeper into the

research and open new perspectives of thoracicradiology as well as oering the most relevantand practical education, said Im.

WCTI 2013 is being jointly organized by theFleischner Society, the Society of Thoracic Radi-ology (STR), the European Society of ThoracicImaging (ESTI), the Japanese Society of Tho-racic Radiology (JSTR), and the Korean Societyof Thoracic Radiology (KSTR). Online registra-tion will be available until April 30, 2013, on theWCTI website (hp://www.wcti2013.org). FromMay 1, 2013, on-site registration is required.

Seoul will play host to WCTI 2013.

About 1,600 participants

from 50 countries are

expected to aend


30/32

30 April 2013 Ca lendar

April21st European Congress of Psychiatry6/4/2013 to 9/4/2013

Location: Nice, FranceInfo: European Psychiatric Association

Tel: (33) 3 8823 9930

Email: [email protected]: www.epa-congress.org

European Congress on Osteoporosis andOsteoarthritis17/4/2013 to 20/4/2013

Location: Rome, Italy

Info: International Osteoporosis Foundation

Tel: (32) 4 254 1225Email: [email protected]

Website: www.ecceo13-iof.org

5th International Congress of Prediabetes andMetabolic Syndrome18/4/2013 to 20/4/2013

Location: Vienna, Austria

Info: Kenes International

Tel: (41) 22 908 0488Fax: (41) 22 906 9140

E-mail: [email protected]

Website: www.kenes.com/prediabetes

48th Annual Meeting of the European Associationfor the Study of the Liver

24/4/2013 to 28/4/2013Location: Amsterdam, NetherlandsInfo: European Association for the Study of the Liver

Tel. (41) 22 807 03 60

Fax. (41) 22 328 07 24

Email: [email protected]

Website : www.easl.eu

5th Association of Southeast Asian PainSocieties Conference28/4/2013 to 5/5/2013Location: Singapore

Info: Pain Association of SingaporeTel: (65) 6292 4710

Fax: (65) 6292 4721Email: [email protected]

Website: www.aseaps2013.org

MAYAmerican Urology Association (AUA) AnnualMeeting4/5/2013 to 8/5/2013

Location: San Diego, California, US

Info: AUA

Tel: (1) 410 689 3700Fax: (1) 410 689 3800


Website: www.aua2013.org

Diabetes Preventing the Preventables Forum24/5/2013 to 26/5/2013

Location: Kuala Lumpur, Malaysia

Info: Asia Diabetes FoundationTel: (852) 2637 6624

Fax: (852) 2647 6624


Website: www.adf.org.hk/dpp2013

12th Congress of the European Association forPalliative Care30/5/2013 to 2/6/2013Location: Prague, Czech Republic

Info: European Association for Palliative Care


31/32

31 April 2013 Humor

Its definitely your appendix. But if you want a second opinion...

I recommend you stay away from food for a while!

Dont worry, if afterwardsyou wake up, it means theoperation was a success!

Youve got to believe meMrs. Capulco. Aging is

definitely hereditary.Your father had it andyour mother had it!

This medication may acceleratethe chances of you having a

stroke, but it will take your mindoff your cellulite problem!

The doctor wont be long.

In the meantime, I would like youto fill out these forms!!

This new diet is definitely working.You only gained 20 kilos!


32/32

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