medical tribune april 2013
TRANSCRIPT
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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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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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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
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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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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.
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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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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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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.
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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.
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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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16 April 2013 Conference Coverage
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
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17 April 2013 Conference Coverage
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
Asian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand
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18 April 2013 Conference Coverage
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
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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.
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20 April 2013 Conference Coverage
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.
Asian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand
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21 April 2013 Conference Coverage
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.
Asian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand
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22 April 2013 Conference Coverage
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
Asian Pacific Society of Cardiology Congress, February 21-24, Pattaya, Thailand
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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).
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24 April 2013 Research Reviews
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
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25 April 2013 Research Reviews
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
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26 April 2013 Research Reviews
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).
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27 April 2013 Research Reviews
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).
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28 April 2013 Research Reviews
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).
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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
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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
Email: [email protected]
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
Email: [email protected]
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
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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!
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