medical tribune january 2013 id
TRANSCRIPT
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January 2013
www.medicaltribune.com
Managing COPD in
primary care
TB in children: We need
to do more
FORUM
Rapid TB test performs
well
CONFERENCE
IN PRACTICE
AFTER HOURS
Hospital Chefs
serve up healthygourmet on a tray
New advisory recommends fewer GERD
endoscopies
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2 January 2013
New advisory recommends fewer GERD
endoscopies
Radha Chitale
New recommendations for patients
with gastroesophageal reux disease
(GERD) advise physicians to avoid
unnecessary endoscopies in patients for whom
there is lile benet.
Upper endoscopy is a routine procedure forGERD diagnosis and management, particular-
ly when monitoring for abnormal or cancerous
esophageal tissue, but overuse results in higher
healthcare costs and adverse side eects with-
out improved patient outcomes.
Limited data suggest that clinicians who
care for patients with GERD symptoms oen
do not follow suggested practice, according
to the Clinical Guidelines Commiee of theAmerican College of Physicians.
The Commiee noted that 10-40 percent of
upper endoscopies are not generally indicat-
ed but are performed for patients with GERD
symptoms without additional dysplasia, are
performed too oen, or are performed before
alarm symptoms occur.
The best practice recommendations indicate
upper endoscopy for patients with heartburnand alarm symptoms including dysphagia,
bleeding, anemia, weight loss or recurrent
vomiting. [Ann Intern Med 2012;157:808-816]
Upper endoscopy is also indicated for pa-
tients who persist with GERD symptoms even
aer a 4-8 week course of acid-reducing pro-
ton pump inhibitor therapy, who persist with
severe esophagitis, or who have a history of a
narrowed esophagus.
Persistent GERD can lead to Barres
esophagus, in which the esophageal lining
erodes and is replaced by stomach lining tis-
sue, and both are associated with increased
risk of esophageal adenocarcinoma. Howev-
er, 80 percent of all cancers occur in men, so
screening for cancer or Barres esophagus
via endoscopy is recommended for men over
50 with GERD.If endoscopic screening of patients with
GERD symptoms is to be pursued, men older
than 50 years will provide the highest yield
of both Barres esophagus and early adeno-
carcinoma, the researchers said.
But both men and women with a history
of Barres esophagus may be screened ev-
ery 3-5 years via endoscopy for dysplasia or
cancerous cells.Up to 85 percent of GERD patients have
non-erosive reux disease.
And while upper endoscopy is a relatively
low-risk procedure, it can cause respiratory
failure, hypotension, reactions to anesthet-
ics, and in extreme cases, perforation and
cardiovascular events.
The commiee based their recommenda-
tions on a literature review and comparisonof clinical guidelines from other professional
organizations.
Because of its high prevalence in the gen-
eral population, care of patients with GERD
is largely within the domain of primary care
providers, they said. Upper endoscopy is
not an appropriate rst step in most patients
with GERD symptoms and is indicated only
when empirical PPI therapy for 4-8 weeks is
unsuccessful.
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3 January 2013
Blood protein resistin reduces statin effect
in obese
Rajesh Kumar
Canadian researchers have identied aprotein called resistin, secreted by fattissue, as the cause of elevated low-density
lipoprotein (LDL) in obese people.
Their research, presented at the Canadian
Cardiovascular Congress recently held inToronto, Ontario, Canada, has shown that
resistin increases the production of LDL in
human liver cells and also degrades LDL re-
ceptors in the liver. As a result, the liver is less
able to clear LDL from the body.
Resistin also reduces the ecacy of statins,
so much so that a staggering 40 percent of pa-
tients taking statins cannot lower their blood
LDL, said senior author Dr. Shirya Rashid,assistant professor in the department of med-
icine at McMaster University in Hamilton,
Ontario, Canada.
The bigger implication of our results
is that high blood resistin levels may be
the cause of the inability of statins to lower
patients LDL cholesterol, said Rashid, add-
ing that the discovery could lead to revolu-
tionary new therapeutic drugs, especiallythose that target and inhibit resistin and
thereby increase the eectiveness of statins.
Dr. Goh Ping Ping, medical director of the
Singapore Heart Foundation, termed the re-
search ndings as progressive medical evi-
dence saying they reinforce the importance
of treating cholesterol levels to goal in orderto reduce cardiovascular risk.
[But] this can be challenging in some
high-risk patients whose target cholesterol
level has to be very low. Hence, we wel-
come new developments in medical thera-
py to help patients reach their target levels
safely, said Goh. As physicians, we need
to also continuously motivate patients
to exercise and adhere to a heart healthydiet.
High resistin levels may aenuate the LDL cholesterol-lowering eectsof statins.
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4 January 2013 Forum
TB in children: We need to do more
Excerpted from a presentation by Dr. Anneke Hesseling, director of the Paediatric TB Research
Program at the Desmond Tutu TB Centre at Stellenbosch University in Cape Town, South
Africa, during the 43rd Union World Conference on Lung Health, held recently in Kuala
Lumpur, Malaysia.
showed that only 1.6 percent of 4,821 cases ofchild TB were registered with the NTP there.[BMC Public Health 2011;11:784]
Despite available therapies, children havebeen systematically neglected in a way thathas led to preventable morbidity and mortal-ity.
ProgressThe good news is that for the rst time,
childhood TB is on the public health agenda,with strong leadership from the WHO andother dedicated groups.
Children have been included in guidelinesfor NTPs and these have been updated in thelast several years including reporting prac-tices, dosage revision for young children to
avoid hepatotoxicity, and guidance on man-aging TB/HIV co-infections.
It is estimated that 500,000 children becomeill with tuberculosis (TB) and that 70,000 af-fected children die annually, but these g-
ures still do not reect the true global burden
of TB.Childhood TB is an indication of recenttransmission, as children tend to acquire theinfection in the rst year of life, and as suchis an indication of household dynamics andepidemiology, especially the emergence ofdrug resistance in the community.
Therefore, TB in children is a litmus testindicating how well we are doing with TBcontrol, and clearly we are failing.
Historical approach
The traditional approach to childhood TBhas been the assumption that proper iden-tication and treatment of infectious adultcases will prevent childhood TB.
But children are not the same as smalladults. They have a developing immune sys-tem, which makes them especially suscep-
tible to severe forms of TB such as TB men-ingitis.
And childhood TB is typically a low-priority disease for national tuberculosisprograms (NTP) because it is dicult to di-agnose with a smear test, it is not usually in-fectious, there are limited resources to tackleTB treatment, and there are a lack of record-ing and reporting approaches. Only abouttwo-thirds of cases are actually notied toNTPs.
A cross-sectional study from Indonesia
A childs developing immune system makes them susceptible to forms ofTB.
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5 January 2013 Forum
However, despite good policies, imple-mentation can be an issue, especially givenlooming funding decits, which aect coun-tries with limited resources in particular.
Some methods to combat these barrierswould be to integrate families in childhoodTB care, including pregnant women andthose with HIV infection, in order to con-solidate services. Every clinic visit should bean opportunity to ask about a household TBcontact.
Empowering healthcare workers at all lev-els to get involved in TB care can yield bet-ter disease reporting statistics. A program infour hospitals in Jakarta, Indonesia, showedthat TB diagnosis rates were similar betweennurses, general practitioners and pediatri-cians when they received specic training.
Pragmatic, simple models of care shouldbe implemented where possible.
In one study, directly observed once-weekly treatments for 12 weeks with a com-
bination of rifapentine and isoniazid was
as eective in adults, if not more, as dailyisoniazid-only therapy for 9 months, whichcould be a beer model for treating children.[N Engl J Med 2011;365:2155-2166]
Partnerships and collaborations with in-dustry could also help improve drug avail-ability and make available new pediatricrst-line xed dose combinations. But forthis market research on barriers to treatment,current practice for uptake and accurate esti-mates on childhood TB to quantify the mar-ket are required.
For the global TB community, seing
short- to medium- and long-term goals, andbeing accountable for them, will help us see
where we are going and be honest about as-sessing achievements and failures.
Research
A decade ago, we did not have any newanti-TB drugs. In children, there was limit-ed evidence for rational TB drug use. Therewere few rapid diagnostic tests, especiallyfor smear-negative TB and drug-resistantTB, and there were no TB vaccines in humantrials.
So we really have come a long way, butthere are still considerable gaps in TB re-search.
Drug formulations tend not to be child-friendly they are unpalatable and dicultto give in accurate doses since tablets must
be broken.However, research has shown that indi-
vidualized tailored treatment can dramati-cally improve outcomes, even among thosewith drug-resistant TB more than 80 per-cent of children with multi-drug resistant TB
can achieve favorable outcomes, even in thecontext of HIV positivity. [Clin Infect Dis 2012
Jan 15;54:157-166]However, these regimens are not eas-
ily handled. Requiring injections, they workbeer in older children and some therapiescan cause signicant hearing loss.
More research is required to develop safermulti-drug resistant TB therapy regimes that
are shorter and easier to use. No rigorous ev-idence-based management for drug-resistantTB preventive therapy is available for adults,much less for children.
Trials to evaluate new therapies and re-gimes should include children and adults.
DiagnosticsThe challenges in TB diagnosis, which
tends to be underfunded, have been a big
burden for recognizing TB in the publichealth framework.
Despite available
therapies, children have been
systematically neglected
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6 January 2013 Forum
It does not help that the reference stan-
dard liquid culture is imperfect in chil-
dren and misses a large portion of children
with clinical disease that isnt bacteriologi-
cally proven.Children are usually an aerthought
when new diagnostics get implemented and
evaluated. However, childhood TB naturally
presents with fewer bacterial units.
Sometimes the TB community has been its
own worst enemy by making the situation
more complicated than it is. In fact, children
should be managed on a daily basis to help
demystify diagnosis and make it more acces-
sible.
New technologies that analyze DNA slash
time to diagnosis and are beer at recog-
nizing TB and drug-resistant TB, even in
children.
ConclusionChildhood TB is coming of age and we
are at a unique juncture of increased public
health awareness, advocacy and funding for
clinical and implementation research.
Last year, World TB Day focused on
children, an indication that the eld is mov-
ing forward. More progress will require
working together in a sustained manner,
monitoring progress in order to reach the
nal goal, which is a generation of children
free of TB.
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7 January 2013 Conference Coverage43rd Union World Conference on Lung Health, 13-17 November, Kuala Lumpur, Malaysia Radha Chitale
reports
New TB therapies offer hope
Two promising new agents under de-
velopment for treating multiple drug-
resistant tuberculosis (MDR-TB) cant
be deployed fast enough, experts say.
The US Food and Drug Administration
(FDA) Anti-Infective Drugs Advisory Com-
miee has approved a request for accelerated
approval of drug-maker Janssens investiga-
tional agent bedaquiline for MDR-TB.
Interim results of a randomized controlled
phase II trial showed that the addition of be-
daquiline to a ve-drug background regimen
(standard second-line drugs) for 24 weeks im-
proved the rate of sputum culture conversion
(shi from positive to negativeMycobacterium
tuberculosis growth) in MDR-TB patients in a
shorter time compared with the background
regimen plus placebo (79 percent vs 58 per-
cent, respectively). The eects of bedaquiline
were durable out to a follow-up assessment
at 72 weeks.
Meanwhile, Otsuka Pharmaceuticals
Group has led for approval of another new
TB agent delamanid with the European
Medicines Agency (EMA).Delamanid has demonstrated increased
sputum culture conversion at 2 months
among patients with MDR-TB compared
with placebo (45.4 percent vs 29.6 percent,
respectively), plus background therapy for
both groups, in a randomized controlled tri-
al. [N Engl J Med 2012;366:2151-2160]
Despite the possibility of approval of these
new agents in the US and Europe, some arefrustrated by the prospect of the lengthy up-
take process required to get new therapies to
where they are really needed.
Geing [drugs] approved in the US where
we only have 130 cases of MDR-TB a year is
really not going to be the place where these
drugs are going to make the biggest dier-
ence, said Mr. Mark Harrington, executive
director of the HIV/AIDS policy think tank
Treatment Action Group.
Countries that have weak regulatory
systems are going to need a lot of political
will and community demand to drive accep-
tance... On the ground youre going to need
regulators, implementers and activists to
work together to speed up not only the de-
mand for the approved drugs but protocol
review for experiments.
Where normal treatment for drug-resis-
tant TB requires a barrage of drugs for up to
2 years or more, novel drug regimens could
shorten treatment courses and improve out-
comes.
But the time required for approval and
implementation of a novel regimen against
MDR-TB, one that would likely include beda-quiline and delamanid together, may prompt
rapid implementation without regulatory go-
ahead.
I think the issue is what to do until we
have beer denitive evidence of a shorter
regimen, said Dr. Mary Edginton of the
University of the Witwatersrand School of
Public Health in Johannesburg, South Africa.
There doesnt seem to me to be any reasonnot to use the short course regimens, under
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8 January 2013 Conference Coverage
research conditions, with informed consent
of patients, and monitored and reported.
Were going to need to pick up the pace,
said Dr. Kenneth Castro, director of the Divi-
sion of TB Elimination at the US Centers forDisease Control and Prevention. The times
of waiting for the best possible evidence to
formulate some early or preliminary recom-
mendations are gone.
Of about 9 million cases of TB globally,
about 630,000 are resistant to treatment, and
440,000 people with MDR-TB die each yearaccording to the WHO Global Tuberculosis
Report 2012.
Intense antibiotic therapy may benefit TB
meningitis patientsAn intensied antibiotic treatment regi-men could improve outcomes in patientswith tubercular (TB) meningitis, according to
an Indonesian study.
We feel that our results challenge the cur-
rent treatment model, said lead researcher
Dr. Rovina Ruslami, of Padjadjaran Univer-
sity in Bandung, West Java, Indonesia.No optimal regimen for TB meningitis ex-
ists. However, as the pathophysiology of TB
meningitis diers from pulmonary tubercu-
losis, Ruslami and colleagues have suggested
that a higher drug dose may garner beer
treatment outcomes.
In their open-label, phase II trial, 60 pa-
tients were randomized to receive a standard
dose (450 mg orally) or high dose (600 mg in-travenously) of rifampicin, aer which they
were divided again into groups to receive
none, 400 mg, or 800 mg of oral moxioxacin
for 2 weeks, aer which patients continued
with standard tuberculosis treatment.
Most patients were young (median age 28
years) and with advanced disease.
Throughout the trial, patients received iso-
niazid and pyrazinamide, which penetrate
well into the cerebrospinal uid (CSF), and
adjunctive corticosteroids.
High-dose rifampicin tripled plasma and
CSF concentrations compared with those seenwith the standard dose (p
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9 January 2013 Conference Coverage
the researchers said.
Ruslami noted that TB meningitis is rare
but can be severe and has high mortality; over
50 percent of patients die even when they
complete treatment.In the current study, half of the patients
died within 6 months, many within the rst
month, mostly due to respiratory failure and
neurological deterioration.
However, the rate of adverse events was no
more than that of standard therapy, Ruslami
said, and the mortality was lower in the high-
dose rifampicin group 34 percent vs 65 per-
cent in the standard therapy group. Moxioxa-
cin did not appear to aect mortality.
Rifampicin is still an appealing drug fortuberculosis, especially in developing coun-
tries since it is cheap, accessible, well toler-
ated, and physicians are aware of it, Ruslami
said, adding that dening the optimum regi-
men from such drugs could help control TB
meningitis in areas of need.
Rapid TB test performs well onsite
Laboratory diagnosis of tuberculosis (TB)improved by 50 percent when a novelrapid DNA test was added to standard spu-
tum smear microscopy.
When used alone, the Xpert MTB/RIF rap-
id DNA test improved diagnosis by 41 per-cent compared with microscopy, according
to data presented by the international group
Medicines Sans Frontieres (MSF).
Culture is the current gold standard for
denitive TB diagnosis, but results can take
up to 6 weeks. However, the Xpert test can
return results within 2 hours.
The rapid assay can also distinguish bacte-
ria resistant to rifampicin, a rst-line TB drug,as well as non-tubercular mycobacteria.
For drug-sensitive TB, based on Xpert,
people can be put on treatment, said Dr. Mar-
tina Casenghi, research advisor with MSFs
Campaign for Access to Essential Medicines.
For drug-resistant TB... in high multiple
drug-resistant TB (MDR-TB) seings, you can
start patients on an optimized regimen and
then send them for a full drug sensitivity test-
ing to tailor the regimen.
MDR-TB diagnosis in low-burden seings
still necessitates a conrmatory culture for ri-
fampicin resistance, she noted.
The Xpert test is a semi-automated DNA
assay in a closed system. A technician pre-
pares a sputum sample with reagents in a car-
A new rapid TB diagnostic test has been rolled out in various locationsaround the world.
Photocredit:WHO
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10 January 2013 Conference Coverage
tridge and loads it into the machine, which is
about the size of a microwave. The machine
costs US$17,000 and each cartridge costs
US$10.
The process limits contamination and re-turns fewer false-positive results as well as
minimizing the skill set required to do diag-
nostic testing.
The Xpert was rolled out in 25 locations
around the world, including one site each in
Vietnam and Myanmar. Some sites were in
high burden MDR-TB locations, some used
Xpert together with sputum culture or mi-
croscopy, some used Xpert alone and some
reported results in children. The total num-
ber of samples was 36,540.
When we added expert to microscopy we
had a relative gain of 50 percent in detection
of TB, said presenter Dr. Elisa Ardizzoni of
the Mycobacteriology Unit of the Institute of
Tropical Medicine in Antwerp, Belgium.
The data included a relatively large numberof inconclusive results from Xpert, almost 7
percent among the whole data set. Howev-
er, these decreased over the 18-month data
gathering period as technicians became more
skilled and new cartridges became available.
Although the benets of the Xpert test do
not exclude the need for beer point of care
tests in peripheral, resource-poor seings,
Casenghi said it is a step in the right direc-
tion to have a simple, fast test that returns
good results in TB endemic countries with-
out requiring extensive infrastructure.
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11 January 2013 Conference Coverage
Interview with the Presidents
8th International Symposium on Respiratory Diseases and American Thoracic Society in China Forum, 8-11
November, Shanghai, China Chuah Su Ping reports
MT: How will the updated Global Initia-
tive for COPD (GOLD) guidelines aect
current clinical practice?
Kra: The main dierence is the criteria for
diagnoses [of COPD]. Theyre quite dierent
from previous versions and we are current-
ly in an adjustment period trying to beerunderstand how to best apply these guide-
lines in practice. The denitions of dierent
severities of COPD have also changed.
MT: How has respiratory clinical practice
today evolved to improve quality of care
for patients, in particular the use of tele-
medicine?
Bai: This year we will be introducing del-egates to what I like to refer to as the Med-
ical Internet of Things, which is basically
a combination of electronic medicine plus
mobile health, or telemedicine. This has
already started being implemented for pa-
tients being treated for sleep apnea [in Chi-
na] and enables a doctor in a clinic or hospi-
tal to monitor a patient who is at home. The
idea is for patients to take home a portable
monitor and the data will be sent directly to
the doctors oce. In some cases, this data
may enable doctors to make a preliminary
diagnosis. Doctors are also able to feedback
directly to patients via the internet upon
receiving the results. This technology will
allow data to be monitored and recorded
while the patient is asleep at home, which isvery useful in the diagnosis and treatment
of sleep apnea.
Kra: I think telemedicine is still an evolv-
ing eld, and I am still skeptical as to how
it will be applied to clinical practice in the
long term. This is an area we still need to
explore in greater detail.
MT: What do you think are the implica-tions of the results from two early-phase
clinical trials [NEJM 2012;366:2443-54,
NEJM 2012;366:2455-65] presented at the
2012 ASCO meeting which provide further
evidence on the role of the immune system
in treating patients with NSCLC?
Bai: I do believe the immune system plays
an important role in lung cancer treatment.
In China, there is ongoing research looking
into the development of a vaccine for [non-
The 8th International Society for Respiratory Disorders (ISRD)
annual meeting marked the inaugural joint scientic session
between the ISRD and the American Thoracic Society (ATS).
Medical Tribune spoke to the leadership of both organizations
- Professor Chunxue Bai, president of the 8th ISRD and ATS in
China Forum, and Dr. Monica Kra, president of the ATS - to
gain their views on key topics in respiratory diseases.
ProfessorChunxue Bai
Dr. Monica Kra
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12 January 2013 Conference Coverage
small-cell lung cancer (NSCLC)]. However,
at the end of the day, early diagnosis of lung
cancer is key to extending patient survival.
Kra: Lung cancer remains a very challeng-
ing area, but I think weve made some prog-ress in recent years. Its exciting that we have
discovered specic biomarkers and paerns
of gene expression which are associated
with response to specic chemo-therapeutic
agents, as this can help us ensure patients
are receiving the right combination of medi-
cation. In other words we are geing closerto the goal of personalized therapy in lung
cancer.
Towards targeted COPD treatment
Chronic obstructive pulmonary disease(COPD) treatment should be individual-ized based on each patients clinical pheno-
type, says an expert.
To do so, we would need to move away
from the traditional assessment of COPD and
its treatment, said Professor Paul W. Jones,
professor of respiratory medicine and head of
the division of clinical science at St. Georges,
University of London, UK.One of the key updates to the Global Ini-
tiative for COPD (GOLD) guidelines last year
was when we categorized the treatment aims
[for COPD] into two groups symptomatic
benet and risk reduction, said Jones, who is
a member of the GOLD Science Commiee.
Symptomatic benet includes relief of symp-
toms, improvement in exercise tolerance and
health status whereas risk reduction includesprevention of exacerbations and disease pro-
gression, and reduction in mortality. This
was a big step forward as we explicitly started
to recognize that the manifestations of COPD
dier between individual patients.
In the Evaluation of COPD Longitudinally
to Identify Predictive Surrogate Endpoints
(ECLIPSE) study, Hurst JR et al observed, over
a 3-year period, that 71 percent of frequent ex-
acerbators in years 1 and 2 were frequent ex-
acerbators in year 3, whereas, approximately70 percent of patients who had no exacerba-
tions in years 1 and 2 had no exacerbations
in year 3. Thus, they concluded that the sin-
gle best predictor of exacerbations, across all
GOLD stages, was a history of exacerbations.
[N Engl J Med 2010;363:1128-38]
In this years GOLD [2012] update, we
also recognize that hospitalization is a very
important risk factor. If a patient has hadone or more hospitalizations in a year, that
automatically places them in a high-risk
category, said Jones.
In 1997, Jones and Bosh published a study
in which they observed that the patients es-
timate of treatment ecacy correlated with
changes in the St. Georges Respiratory Ques-
tionnaire (SGRQ) score.
If the patients judged their treatmentas ineective, that correlated with a worse
SGRQ score. However, if they judged their
treatment as eective or very eective, the
improvement in SGRQ score was either at
the threshold of clinical signicance or bet-
ter, said Jones. [Am J Respir Crit Care Med
1997;155:1283-1289]
These ndings are signicant as they tell
us that the patients personal feedback should
also be taken into consideration.
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Highlighting a recent study by Mahler DA
et al, Jones noted that when indacaterol was
added to tiotropium, there was a signicantly
greater change in symptoms compared with
patients on tiotropium alone. These resultsare in line with the COPD guideline recom-
mendations to combine bronchodilators with
dierent mechanism of actions, in this case a
long-acting beta agonist and long-acting mus-
carinic antagonist. [Thorax 2012;67:781-788]
In treating COPD, one of the key things
to remember is to treat, to improve the pa-
tients symptoms and reduce exacerbations,Jones said. Physicians can then custom-
ize treatment based on the patients clinical
phenotype.
NIPPV for treating COPD exacerbations
Non-invasive positive pressure venti-lation (NIPPV) is currently the pre-eminent established application in acute
respiratory failure of chronic obstructive
pulmonary disease (COPD) exacerbations,
but experts say skilled application is critical
for patient breathing.
The rationale for selecting NIPPV is to
rst of all reduce the patients breathingworkload, said Dr. Giuseppe A. Marraro,
director of the Anesthesia and Intensive Care
Department at the A.O. Fatebenefratelli and
Ophthalmiatric Hospital in Milan, Italy, and
this procedure can improve gas exchange,
reduce endotracheal intubation, reduce in-
fection rate and increase patient survival.
[Lancet 2009;374:250]
These are all key factors which willeventually determine treatment success in
patients with COPD exacerbations.
But he noted that patient collaboration
and the skill of hospital sta can play a ma-
jor role in how eective NIPPV will be.
Compared with conventional ventila-
tion, NIPPV confers a higher risk of mask
dislodgment and there is a need for higher
ventilator pressure, said Marraro. He high-
lighted that NIPPV is contraindicated in pa-
tients who require more than 50 percent oxy-
gen; with signicant hypotension induced
by conventional ventilator therapy; with
fractured skull base, facial fractures and in-
creased intracranial pressure; and with re-
spiratory arrest.
Marraro cautioned that NIPPV should
be discontinued if there is no improvement
in gas exchange or dyspnea, or if there is aneed for endotracheal intubation to man-
age secretions or protect the airway. Stop
NIPPV immediately if the patient exhibits
coordinative problems, reduced conscious-
ness and increasing levels of carbon diox-
ide coupled with decreasing pH levels, he
stressed.
Patients with COPD who have exacerba-
tions of respiratory failure can benet sig-nicantly from ventilator assistance.
NIPPV has been shown to reduce the se-
verity of breathlessness within the rst four
hours of treatment, decrease the length of
hospital stay and reduce the rates of mortal-
ity and intubation, said Marraro. He noted
that the advantages of NIPPV include the
avoidance of intubation, which is typically
necessary for 16-35 percent of acute COPD
exacerbations and carries its own complica-
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14 January 2013 Conference Coverage
tions.
NIPPV preserves the patients ability to
cough, speak and swallow. It can also be
used away from the ICU, thereby potentially
reducing costs.With NIPPV, physicians have the choice
of selecting either a nasal or facial mask for
their patients. The advantages of the nasal
mask are that it is less claustrophobic and al-
lows the patient to speak, expectorate, vom-
it, and ingest orally. The facial mask on the
other hand, may be more useful for dyspneic
patients who are usually mouth breathers,
said Marraro. NIPPV can be applied in
appropriate non-ICU seings but it is impor-tant to take into consideration the patients
personal feedback as well as the need for
fully trained and experienced hospital sta
and appropriate equipment, monitoring and
support.
OSA linked to glucose dysmetabolism
Accumulating evidence suggests that
obstructive sleep apnea (OSA) is as-
sociated with glucose dysmetabo-
lism, says an expert.
While the link remains controversial,
it is clear that both conditions are related to
obesity, said Professor Mary Ip of the Uni-versity of Hong Kong. OSA may also have
a causal role on increasing insulin resistance,
glucose tolerance and type 2 diabetes mellitus
[T2DM].
There have been many studies examin-
ing the relationship between insulin resis-
tance and OSA, but few studies on the role
of B-cell dysfunction in OSA, noted Ip. One
such study by Punjabi NM et al showed thatsevere OSA is associated with impaired B-
cell dysfunction. [Am J Respir Crit Care Med
2009;179:235-240] This reduces the compen-
satory insulin secretion, leading to the devel-
opment of glucose intolerance or diabetes,
said Ip.
In the Sleep Heart Health Study, Seicean S
et al found that OSA may be independently
associated with various states of glucose me-
tabolism including impaired fasting glucose,
impaired glucose tolerance and occult diabe-
tes. [Diabetes Care 2008;31:1001-1007]
CPAP has been shown to improve insulin sensitivity in non-diabeticpatients.
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15 January 2013 Conference Coverage
Similarly, a study in Hong Kong showed
that OSA was independently associated
with metabolic syndrome, hypertension and
[increased] waist circumference, said Ip.
[Respir Med 2006;100:980-987]More recent studies in Japan and China
have also shown that patients with severe OSA
had a higher prevalence of hypertension, dys-
lipidemia, glucose intolerance and metabolic
abnormalities. [Respirology 2010;15:1122-1126,
Sleep Breath 2012;16:571-578]
Continuous positive airway pressure
(CPAP) treatment for OSA has been shown
to improve insulin sensitivity in non-diabetic
patients with BMI less than 30 kg/m2. [Am J
Respir Crit Care Med 2004;169:152-62] However,
the eects of CPAP treatment in patients with
T2DM remains controversial, Ip said.
Many studies have been carried out to ex-
amine the eect of CPAP treatment of OSA in
patients with T2DM, however, most did not
report any signicant dierence on glycemic
control [post-treatment], she said. Compli-ance to CPAP may also play an important
role in improving insulin resistance in OSA
patients. The use of CPAP to improve insu-
lin sensitivity in OSA patients remains to be
validated.
While convincing data demonstrate a link
between OSA and B-cell dysfunction, insulin
resistance, metabolic syndrome and increas-
ing HbA1c levels, lile is known about the
long-term outcomes of OSA treatment for
T2DM, which Ip said would be a key area for
future research.
CPAP may improve cognitive function inOSA patients
Continuous positive airway pressure(CPAP) treatment for obstructive sleepapnea (OSA) may improve neurocognitive
function, show the latest results from the
Apnea Positive Pressure Long-Term Ecacy
Study (APPLES).Up till recently, there have been studies
examining the eect of sleep apnea on neu-
rocognitive function said Professor Clete A.
Kushida of Stanford University Medical Cen-
ter in Stanford, California, US.
Previous studies, however, have been lim-
ited by relatively small sample sizes, noncom-
prehensive test baeries and inadequate con-
trol groups. [J Clin Sleep Med 2006;2:288-300]
In APPLES, Kushida and his team random-
ized 1,100 OSA patients to receive either active
CPAP or its sham version to test the hypoth-
eses that hypoxemia and/or sleepiness in OSA
is responsible for neurocognitive decline.
The main aims of the study were to identi-
fy specic decits in neurocognitive functionin a large heterogenous population of OSA
patients and to assess the long-term eec-
tiveness of CPAP therapy on neurocognition,
mood, sleepiness and quality of life. It also
sought to evaluate which decits are revers-
ible and most sensitive to the eects of CPAP.
[J Clin Sleep Med 2006;2:288-300]
The primary outcomes examined were
aention and psychomotor function; learn-
ing and memory (L/M); and executive and
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16 January 2013 Conference Coverage
READ JPOG ANYTIME, ANYWHERE.Download the digital edition today at www.jpog.com
frontal-lobe function (E/F). These were ex-
amined via the Pathnder Number (PN) Test,
the Buschke Selective Reminding Test (BSRT),
and the Sustained Working Memory Test
(SWMT), respectively, said Kushida, who isalso president of the World Sleep Federation.
While covariate-adjusted analyses re-
vealed no signicant dierences in the PN
and BSRT test results between the active
CPAP and sham group, we did nd signi-
cantly beer SWMT results, which examined
E/F, in the active CPAP group, he said. Low-
er levels of oxygen saturation and increased
sleepiness also produced signicant eects on
the E/F test.
However, these eects were only de-
tected at 2 months and were minor com-
pared with the eects of caeine and
diphenhydramine for this measure in other
studies, he noted.
Interestingly, the study also reported that
adherence to CPAP was signicantly lower in
the sham group, and this, said Kushida, was a
major limitation in APPLES.
Interpreting APPLES
The detection of CPAP eects in the pri-
mary E/F variable suggests that the SWMT
test - in which a cognitive task is combined
with simultaneous electroencephalographicmeasures of brain function - is a more sen-
sitive measure for subtle neurocognitive
changes, said Kushida.
The mixed results from prior studies, as
well as the limited eect on CPAP on neuro-
cognition in APPLES, suggest the existence
of a complex OSA-neurocognitive relation-
ship. Clinicians should consider disease
severity, sleepiness, individual dierences
(variability in neurocognitive function and
brain reserve) and treatment adherence
in managing OSA patients with CPAP, he
opined.
Lastly, we need more large-scale sleep
studies to further examine the ecacy or in-
ecacy of CPAP therapy on this very preva-
lent sleep-related breathing disorder.
The results of APPLES are expected to be
published in December 2013.
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17 January 2013 Conference Coverage
Personal Perspectives
In developing the new GOLD guidelines, we set clear treatmentobjectives based on improving symptoms; and for the rst time in
COPD, identifying that risk reduction is a key component in treatment,
particularly in terms of reducing the risk of exacerbations.
Paul W. Jones, University of London, UK
One of the things we need to do is to strengthen the bridge betweenEastern and Western science. Meetings like these not only showcase the
science being done here in China but also facilitate the exchange of ideas
to advance the state of the science globally. As an economist, my interest
lies mainly in the cost-of-care issues of access and delivery systems.
Stephen Crane, Executive Director, American Thoracic Society
The topics of any conference should rst of all reect the prevalenceof the disorders in the [host] country. Sleep apnea, lung cancer and
COPD are all prevalent in China. Second, it should also reect the
emerging science which will aect treatment and diagnosis. Third, it
should support ongoing research within the country. Lastly, it should
also dene what the young physicians will be facing in the future. In
my opinion, the ISRD 2012 has done an excellent job in bringing all that
together.
Teolo Lee-Chiong, University of Colorado, US
Being an international conference with delegates aending from all over
the world, there should be more English speaking sta on hand. Every
time we need any help, we have to go the secretariat oce. Other than
that, everything else was great.
Maulik Sanghvi, India
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18 January 2013 Gastroesophageal Reflux Disease
Rajesh Kumar
Obese individuals can reduce theirrisk of developing gastroesophagealreux disease (GERD) by exercis-
ing even if only once-a-week, according to aSwedish study.
However, no such benet from occasional
physical activity was seen in patients with nor-mal body mass index (BMI). [World J Gastroen-terol 2012;28:3710-3714]
Researchers randomly selected 4,910 peo-ple aged between 40 and 79 years from theSwedish registry of the total population fora cross-sectional survey. Data on their physi-cal activity, GERD, BMI and the covariatesage, gender, comorbidity, education, sleep-ing problems, and tobacco smoking were ob-tained using validated questionnaires.
GERD was self-reported and denedas heartburn or regurgitation at least onceweekly, and the presence of at least moderateproblems from such symptoms. Frequency ofphysical activity was categorized into high(several times/week), intermediate (approxi-mately once weekly) and low (1-3 times amonth or less).
Analyses were stratied for participantswith normal weight (BMI < 25 kg/m2), over-weight (BMI 25 to 30 kg/m2) and obese (BMI> 30 kg/m2). Obese participants were on aver-age slightly older, had fewer years of educa-tion, more comorbidity, slightly more sleepingproblems, lower frequency of physical activity,and higher occurrence of GERD.
In 680 obese individuals, intermediate fre-quency of physical activity was associatedwith a decreased occurrence of GERD com-
pared with low physical activity (adjustedhazard ratio [HR] 0.41). Among the 2,146normal-weight participants, a decreased riskof GERD was seen with higher physical ac-tivity (HR 0.59), but the benet was negatedaer adjusting for potential cofounders suchas sleeping problems and high comorbidity.A similar trend was seen in 1,859 overweight
participants.The studys limitations include an inherent
uncertainty about the accuracy of self-report-ed data and lack of validation of the assess-ment of frequency of physical activity, BMIand possible previous surgical interventionsfor GERD, said the study authors.
Because it is a cross-sectional study, it isnot possible to know if the participants witha self-detected association between reux andphysical exercise may have changed their
behavior, resulting in reverse causality, theysaid.
The current ndings conrm the previouspopulation-based studies assessing an asso-ciation between physical activity and GERDwithin the general population.
However, none of the previous studiesstratied analyses for BMI categories; mean-
ing that the decreased risk of GERD limited toobese individuals is a rst time observation,said authors Dr. Therese Djrv and colleaguesat the department of molecular medicine andsurgery, Karolinska Institutet in Stockholm,Sweden.
Should the present results be conrmed infuture research, the ndings from this studymight be important for the prevention andtreatment of GERD and its complications,they concluded.
Once weekly exercise enough to reduce
GERD risk in obese
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19 January 2013 Gastroesophageal Reflux Disease
Alexandra Kirsten
Aretrospective study has shown thatpatients with type 2 diabetes havetwice the risk of Barres esopha-
gus, a condition where the esophageal lin-ing becomes abnormal, whether or not otherrisk factors such as smoking or obesity were
present.The ndings were presented during the
American College of Gastroenterologys 77thAnnual Scientic Meeting, held recently inLas Vegas, Nevada, US. [Abstract 49]
To determine whether there is an asso-ciation between type 2 diabetes and Barresesophagus, Dr. Prasad Iyer, associate profes-sor of gastroenterology and hepatology at the
Mayo Clinic College of Medicine in Roches-ter, Minnesota, US, and his fellow researchersconducted a population-based, case-controlstudy.
They identied 14,245 patients with Bar-res esophagus and 70,361 control subjectswho were matched for age, sex, enrolmentdate, duration of follow-up, and practice re-gion using the United Kingdoms GeneralPractice Research Database, a primary care
database that includes over 8 million patients.The data showed that patients with Bar-
res esophagus were more likely to havesmoked and consumed alcohol, had a higher
body mass index, and a higher prevalence oftype 2 diabetes than control subjects.
Multivariate analysis showed a 49 per-cent increased risk for Barres esophagus inpatients with type 2 diabetes. The link was
stronger in men (OR, 2.03; 95% CI, 1.01 - 4.04)than in women (OR, 1.37; 95% CI, 0.63 - 2.97).
Interestingly, we found that among thestudy cohort, if you had diabetes there wasa twofold increase in your risk for Barresesophagus, Iyer said. When we stratied
the results by gender, the association of type2 diabetes with Barres esophagus was stron-ger in males compared to females, which mayreect the dierent fat distributions in menand women.
There is some evidence that central obe-sity is a risk factor for Barres esophagusand esophageal cancer through mechanicalor metabolic mechanisms, such as hyperin-sulinemia. The researchers suggested fat in
the abdomen could be a reux-independentmechanism leading to Barres esophaguswhich is known to be a precursor of esopha-geal adenocarcinoma.
If we nd the precursor early enough, wecould put these patients under surveillanceor treat the precursor and reduce the risk,Iyer said. He added that further prospectivestudies are needed to beer understand the
link between Barres esophagus and type 2diabetes.
Barretts esophagus linked to type 2
diabetes
Patients with Barres esophagus were also more likely to have smoked orconsumed alcohol, and had a higher mean BMI than controls.
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20 January 2013 News
Alexandra Kirsten
Toxic smoke and soot from open-
re cooking causes nearly 2 million
deaths each year, primarily among
women and children who spend the most
time at reside, according to the World
Health Organization.
To examine the link between the atmo-
sphere and human health, the US National
Center for Atmospheric Research (NCAR) in
Boulder, Colorado, US, is launching a large-
scale study into the impact of open-re cook-
ing on regional air quality and disease.
Pollutants and particles spewed by open
res are a proven health risk to individuals, to
villages and entire regions, explained NCAR
lead scientist Dr. Christine Wiedinmyer. The
3-year study will be the rst to discuss broad-
scale solutions to disease and pollution from
open-re cooking
The use of wood, animal and agricultural
waste for cooking and warming homes in
developing countries is a principal source
of carbon monoxide, particulates and smog.
These can cause a variety of symptoms, rang-ing from headaches and nausea to conditions
like cardiovascular and respiratory diseases.
The international team of pollution, cli-
mate, and health experts from NCAR, the
University of Colorado Boulder, the Universi-
ty of Ghana School of Public Health and Gha-
na Health Services, will analyze the eects of
smoke from traditional cooking methods on
households, villages, and entire regions.
Given that an estimated 3 billion people
worldwide are cooking over re and smoke,
we need to beer understand how these pol-
lutants are aecting public health as well as
regional air quality and even the climate,
said Wiedinmyer.
The research group will focus on deter-
mining the inuence of traditional cooking
methods on human health using air quality
sensors and computer and statistical models.
They will also evaluate the disease reduc-
tion capacity of low-emission cook stoves and
if these newer, more ecient stoves positively
aect regional air quality. Surveys among vil-lagers on their understanding of the connec-
tion between open-re cooking and disease
will also help gauge their interest in changing
their cooking habits.
The results of the study could point to the
best means for a transition to cleaner cook-
ing methods and show how the open-re
emissions are aecting weather paerns that
contribute to global warming.
Health impact of open-fire cooking to be
studied
The large-scale study will also assess the potential of low-emission cookstoves to reduce disease.
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21 January 2013 News
Rajesh Kumar
Elderly hypertensive patients may be at
higher risk of hip fractures in the rst
45 days aer starting antihypertensive
drug therapy, according to research.
Canadian researchers linked a cohort of
301,591 newly treated hypertensive rest home
residents (mean age, 81 years) to the records
of 1,463 hip fractures between 1 April 2000 to
31 March 2009. They analyzed the risk dur-
ing the rst 45 days following therapy initia-
tion, with equal control periods before and
aer that and a total of 450-day observation
period. [Arch Intern Med2012; doi:10.1001/2013.
jamainternmed.469]
The outcome was the rst occurrence of a
proximal femoral fracture during the risk pe-riod. The researchers found a 43 percent in-
creased risk of having a hip fracture during the
risk period compared with the control periods
(incidence rate ratio [IRR], 1.43; 95% con-
dence interval [CI], 1.19 to 1.72).
Initiating antihypertensive drugs such as
thiazide diuretics, angiotensin II converting
enzyme (ACE) inhibitors, angiotensin II re-
ceptor blockers (ARBs) or calcium channelblockers in the elderly is already associated
with an immediate increased risk of falls. The
study sought to nd out the immediate risk of
hip fracture.
Adjusting for age and use of other medica-
tions implicated in falls, such as psychotropic
drugs, did not change the risk. The relation-
ship was generally consistent for all classes of
antihypertensive drugs (IRRs, 1.30 to 1.58), al-though it reached statistical signicance only
for ACE inhibitors (IRR, 1.53, 95% CI, 1.12 to
2.10) and -blockers (IRR, 1.58, 95% CI, 1.01
to 2.48).
Dr. Kenneth Ng Kwan Chung, cardiolo-
gist at Novena Heart Centre in Singapore,
said physicians know that ACE inhibitors can
cause rst dose hypotension, especially in pa-
tients who are already on diuretics. But it is not
clear why -blockers were also implicated in
the study.
Elderly patients are more likely to have
sick sinus syndrome and -blockers may
cause severe bradycardia and then fainting
and falls [leading to fracture], explained Ng.
Asian patients are usually frailer and
smaller sized than their Western counter-
parts, which might make the eect of anti-
hypertensive medications more marked inthem, he said, adding that physicians should
start with the lowest possible dose of one
medication and rst check for postural hy-
potension, particularly when starting ACE
inhibitors and -blockers in elderly patients.
Check the heart rate before starting
-blockersand educate the patient to get
up slowly out of the bed or chair. Wait for
any giddiness or instability to subside beforetaking the next few steps to walking. Ask a
family member to watch over them when
they get up in the middle of the night, said
Ng.
Patients could also monitor their blood
pressure at home and send the readings to
their family doctor, who can then advise them
on the dose reduction or discontinuation of
the medication if the blood pressure goes toolow, he concluded.
Elderly face higher hip fracture risk after
starting BP drugs
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22 January 2013 News
Rajesh Kumar
In patients with multivessel coronary ar-tery disease, coronary artery bypass gra(CABG) surgery was more eective in an
older cohort, while percutaneous coronaryintervention (PCI) was favored in a relativelyyounger one in a large analysis.
Researchers pooled individual data from7,812 patients who were randomized in 10clinical trials of CABG or PCI to assess whetherpatient age modies the comparative eective-ness of those interventions. [J Am Coll Cardiol2012; 60:2150-2157]
They analyzed age as a continuous vari-able in the primary analysis and divided it intothree groups of 56.2 years, 56.3 to 65.1 years
and 65.2 years for descriptive purposes. Theoutcomes assessed were death, myocardialinfarction and repeat revascularization overcomplete follow-up and angina at 1 year. Old-er patients were more likely to have hyperten-sion, diabetes, and 3-vessel disease comparedwith younger patients (p=0.001 for trend).
Over a median follow-up of 5.9 years, theeect of CABG versus PCI on mortality var-ied according to age (interaction p=0.01), with
adjusted CABG/PCI hazard ratios and 95 per-cent condence intervals of 1.23 (95% CI 0.95 to1.59) in the youngest group; 0.89 (95% CI 0.73to 1.10) in the middle group; and 0.79 (95% CI0.67 to 0.94) in the oldest group.
The CABG/PCI hazard ratio was less than 1for patients 59 years. A similar interaction ofage with treatment was present for the compos-ite outcome of death or myocardial infarction.
In contrast, patient age did not alter the com-parative eectiveness of CABG and PCI on theoutcomes of repeat revascularization or angina.
Dr. Kenneth Ng Kwan Chung, cardiologistat Novena Heart Centre in Singapore, said in-creasing age is known to be a risk factor formortality and complications resulting fromCABG.
Therefore in patients who are elderly, we
sometimes aempt to perform PCI on the ste-notic lesions rather than send them for surgery.However, this study points out that the olderpatients actually benet more from CABGthan PCI. It could be that older patients havemore diuse disease than younger patients.
Ng said the ndings are relevant for Asians aswe have a higher proportion of patients who arediabetic, compared with Caucasians, and havea rapidly aging population in which ischemic
heart disease is the biggest cause of morbidity.The take home message for us is to explain
to the patients aged >59 years that CABG couldbe a beer option than PCI if they have triplevessel disease and diabetes. This is becauseof a 21 percent lower risk of cardiovascularmortality in the >65 years age group in thestudy, he said.
Also, there was no dierence in compli-
cations between the PCI and CABG groupsin terms of death from the procedure andstroke.
CABG more effective than PCI in older
CAD patients
Researchers analyzed pooled data from 10 clinical trials involving patientswho had undergone CABG or PCI.
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23 January 2013 News
Bleeding rates with warfarin much higher
in reality?
Elvira Manzano
The rates of major bleeding with warfa-
rin use in atrial brillation (AF) may be
higher than reported in clinical trials
and are oen fatal, new research suggests.
A population-based study conducted in
Canada involving 125,195 patients who start-
ed warfarin therapy aer a diagnosis of AFshowed an overall rate of hemorrhage of 3.8
percent per person-year over a study period
of 13 years. The risk of major hemorrhage (de-
ned as a visit to an emergency department
or admission to hospital) was highest during
the rst 30 days of treatment (11.8 percent
per person-year). [CMAJ 2012;doi:10.1503/
cmaj.121218]
The results were important as they re-ect the bleeding rates with warfarin in the
real world, said lead study author Assistant
Professor Tara Gomes, of the University of
Toronto in Ontario. These rates are consid-
erably higher than the rates of 1 to 3 percent
per person-year reported in randomized con-
trolled trials of warfarin therapy.
The dierence, she said, may be due to the
strict inclusion criteria and close monitoringof patients in clinical trials and the average
age of participants in their study being older.
Warfarin helps prevent stroke and blood
clots in AF patients. However, it has a nar-
row therapeutic window (international nor-
malized ratio [INR] 3-4) and requires regular
monitoring to minimize the risk of hemor-
rhage. Currently, there are no large trials of-
fering real-world, population based-estimatesof bleeding rates among patients on warfarin.
This prompted Gomes and colleagues
to study the medical records of AF patients
(aged 66 years or older) who started warfarin
therapy between April 1997 and March 2008.
The cumulative incidence of hemorrhage
was 4.1 percent at 1 year and 8.7 percent at5 years. In total, 1,963 patients (18.1 percent)
died in the hospital or a week aer discharge.
Although the rate of intracranial hemorrhage
was low in the study, it was associated with
a high mortality rate (42 percent). As expect-
ed, bleeding rates were higher in those with
a CHADS2 score of 4 or higher (16.7 percent
per person-year) and in patients older than 75
years (4.6 percent per person-year).Our study provides timely estimates of
warfarin-related adverse events that may be
useful to clinicians, patients and policymak-
ers as new options for treatment become
available, Gomes said.
Doctors should know the potential for
bleeding in patients when starting them on
warfarin. However, the decision to shi to
new oral anticoagulants could not be madeon the basis of these data alone, she said.
Real-life bleeding rates associated with warfarin may be much higher thanthose reported in clinical trials.
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24 January 2013 News
Digoxin linked to raised mortality risk in
patients with AF
Rajesh Kumar
Physicians should reassess the role of di-
goxin in the management of atrial bril-
lation (AF) in patients with or without
heart failure (HF), experts warned following
study ndings that link the drug to a signi-
cant increase in mortality in such patients.
Digoxin is widely used around the world
for the treatment of AF and HF. It is extracted
from the foxglove plant (digitalis) and helps
the heart beat stronger and have a more regu-
lar rhythm. However, it has a narrow thera-
peutic index beyond which it can be danger-
ous.
Researchers analyzed data from 4,060 AF
patients who had enrolled in the landmark
AFFIRM* trial to determine the relationship
between digoxin and deaths in this group. [Eur
Heart J2012; doi:10.1093/eurheartj/ehs348]
Digoxin was associated with a 41 percent
increase in all-cause mortality (estimated haz-
ard ratio [EHR], 1.41, 95% condence interval
(CI), 1.19 to 1.67, p
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25 January 2013 Research Reviews
Devices to remove thrombus in acute
ischemic strokeTreatments for acute ischemic stroke includeuse of IV recombinant tissue plasminogen ac-tivator (rt-PA), intra-arterial brinolysis and the
use of mechanical clot-removing devices. Two
new clot-removing devices have been compared
with a currently used device (the Merci Retriever)
in successively reported studies in the Lancet.
The Merci retriever is a exible nitinol wire with
distal corkscrew-shaped coil loops with aached
laments. It is placed distally to the clot to ensnare
and remove the clot into a balloon-guide catheter
in the cervical internal carotid or vertebral arter-
ies. The Trevo Retriever is a new device, a stent
retriever which is placed via a microcatheter. The
stent is opened and the clot is trapped in the stent struts and retrieved into an internal carotid
or vertebral artery catheter. A trial at 26 sites in the US and one in Spain included 178 patients
with large-vessel occlusion acute ischemic stroke. Randomization was to thrombectomy with
one or other of the two devices. A thrombolysis in cerebral infarction (TICI) score of 2 or
greater reperfusion was achieved in 86 percent of patients with the Trevo Retriever and 60
percent with the Merci Retriever, showing the superiority of the Trevo Retriever. Device safety
was similar in the two groups.
The Solitaire Flow Restoration Device is also a self-expanding stent retriever. A trial at 18 US
sites and one in France included 113 patients. A thrombolysis in myocardial infarction (TIMI)
score of 2 or 3 was achieved in 61 percent (Solitaire) vs 24 percent (Merci), showing superiority
of the Solitaire device. A good neurological outcome at 3 months was recorded for 58 percent
vs 33 percent, and 90-day mortality was 17 percent vs 38 percent.The Trevo and Solitaire devices were both beer than the Merci device.
Nogueira RG et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a
randomised trial. Lancet 2012; 380: 123140; Saver JL et al. Solitaire ow restoration device versus the Merci Retriever in patients with acute ischaemic
stroke (SWIFT): a randomised parallel-group, non-inferiority trial. Ibid: 12419; Gorelick PB. Assessment of stent retrievers in acute ischaemic stroke.
Ibid: 120810 (comment).
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26 January 2013 Research Reviews
Predicting CV risk with C-reactive
protein, fibrinogen levelsThere is debate about the usefulness of measuring C-reactive protein and brinogen levelsin healthy people to predict risk of cardiovascular disease. An analysis of 52 prospectivestudies (n=246,669 participants) without known cardiovascular disease has been reported.
It was estimated that the addition of C-reactive protein or brinogen to standard risk factors
would improve the classication of people into low, intermediate or high 10-year risk catego-
ries by 1.52 percent and 0.83 percent, respectively. With appropriate use of statin therapy, the
addition of C-reactive protein and brinogen measurements might prevent 30 cardiovascular
events over 10 years among 100,000 adults aged 40 years or older.
It is concluded that with current treatment guidelines, C-reactive protein or brinogen mea-
surement in people at intermediate cardiovascular risk could help prevent one additional
event over a period of 10 years for every 400 or 500 people screened.
The Emerging Risk Factors Collaboration. C-reactive protein, brinogen, and cardiovascular disease prediction. NEJM 2012; 367: 131020.
Prasugrel vs clopidogrel for ACS without
revascularization
There is uncertainty about optimum platelet inhibition therapy for patients with unstableangina or non-ST-segment elevation myocardial infarction (non-STEMI) who are man-aged without revascularization. A study at 966 sites in 52 countries has shown similar results
with either prasugrel or clopidogrel.
A total of 7,243 patients aged
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27 January 2013 Research Reviews
Perioperative and anesthetic-related
deaths: Systematic review, meta-analysisAsystematic review and meta-analysis has assessed changes in perioperative mortality indeveloped and developing countries over the last 3-4 decades.The study included 87 studies with information about 21.4 million administrations of gen-
eral anesthesia for surgery. Mortality due solely to anesthesia was 375 per million before the1970s, 52 per million in the 1970s and 80s, and 34 per million in the 1990s and 2000s. The cor-responding gures for total perioperative mortality were 10,603, 4,533, and 1,176 per million.The United Nations Human Development Index (HDI), which is based on life expectancy, lit-eracy, further education and income, was used to assess the development status of countries.
There was a signicant relationship between HDI score and perioperative and anesthetic-re-lated mortality. Rates of anesthetic-related mortality fell signicantly in high-HDI (developed)countries but rose in low-HDI (developing) countries. Total perioperative mortality decreasedin both high and low HDI countries but the decrease was slower in low HDI countries. Ratesof cardiac arrest were higher in low HDI countries.
Despite an increase in the number of greater risk patients being operated on, the periopera-tive mortality has decreased signicantly over the last few decades but the decrease has beenslower in developing countries. More aention needs to be given to increasing evidence-based
best practice in developing countries.
Bainbridge D et al. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet
2012; 380: 107581; Avidan MS, Kheterpal S. Perioperative mortality in developed and developing countries. Ibid: 10389 (comment).
Tranexamic acid and death from
traumatic bleeding
Tranexamic acid given within 3 hours of injury reduces mortality in patients with traumatic
bleeding. An analysis of data from an international randomized trial has shown that thebenet from tranexamic acid does not vary with the severity of injury.
The trial included 13,273 patients randomized to tranexamic acid or placebo within 3 hoursof injury and stratied according to risk of death at baseline (50 percent). In these risk strata, the reduction in risk of death with tranexamicacid was 37, 29, 32 and 28 percent, respectively, with no signicant dierence between strata.Treatment with tranexamic acid reduced the risk of arterial, but not venous, thrombosis.
Tranexamic acid given within 3 hours of injury reduces mortality from bleeding at alldegrees of severity of injury.
Roberts I et al. Eect of tranexamic acid on mortality in patients with traumatic bleeding: prespecied analysis of data from randomised controlled trial.
BMJ 2012; 345 (Oct 6): 16 (e5839).
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28 January 2013 Research Reviews
MRI abnormalities in radiologically
normal kneesMany people with knee pain have no abnor-mality on knee X-rays. A US study has shownthat MRI in these circumstances may show abnor-
malities of questionable clinical signicance.
The study, in the Framingham community cohort,
included 710 people aged >50 with normal knee
X-rays. Knee pain in the last month was reported
by 206 people (29 percent). An osteoarthritic ab-
normality was detected by MRI in 631 subjects (89
percent); 524 (74 percent) had osteophytes, and 492
(69 percent) cartilage damage. The frequency of ab-
normalities increased with age. The prevalence of
abnormalities was 90 to 97 percent among subjects
with knee pain and 86 to 88 percent among those
without knee pain.
Osteoarthritic abnormalities on MRI are common
aer the age of 50 whether or not the subject com-
plains of knee pain and are therefore of question-
able clinical signicance.
Guermazi A et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study
(Framingham Osteoarthritis Study) BMJ 2012; 345 (Sept 15): 16 (e5339).
READ JPOG ANYTIME, ANYWHERE.Download the digital edition today at www.jpog.com
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29 January 2013 Research Reviews
Hyperglycemia and hypoglycemia in
critically ill patientsSevere hyperglycemia in patients in the inten-sive care unit (ICU) is associated with increasedmortality. Initial reports suggested that careful
control of blood glucose levels might reduce this
mortality but these ndings have not been con-
rmed in more recent trials.
The Normoglycaemia in Intensive Care Evalua-
tion-Survival using Glucose Algorithm Regulation
(NICE-SUGAR) trial, reported in 2009, showed in-
creased mortality with intensive glucose control.
Other evidence has suggested that hypoglyce-
mia may be the underlying factor. Now a further
analysis of data from the NICE-SUGAR trial has
demonstrated a relationship between moderate or
severe hypoglycemia and mortality.
The NICE-SUGAR study included 6,104 adults
in ICUs in 42 hospitals. The present analysis is of
follow-up data for 6,026 patients among whom 45
percent had moderate hypoglycemia (blood glu-
cose 2.33.9 mmol/L) and 3.7 percent had severe hypoglycemia (2.2 mmol/L or less). Moderate
hypoglycemia occurred in 74 percent of patients in the intensive blood glucose control group
and severe hypoglycemia in 7 percent. Most episodes of severe hypoglycemia (93 percent)
occurred in the intensive control group. Mortality was 28.5 percent among patients with mod-
erate hypoglycemia, 35.4 percent among those with severe hypoglycemia, and 23.5 percent
among those who did not develop hypoglycemia, giving 41 percent and 2.1-fold increase in
risk with moderate and severe hypoglycemia. The risk of death was particularly increased inpatients who had moderate hypoglycemia on more than 1 day, those who had severe hypogly-
cemia without insulin treatment, and those who developed distributive (vasodilated) shock.
Intensive glucose control in ICU patients commonly causes moderate or severe hypoglyce-
mia with an increased risk of death but these data cannot prove a causal relationship between
hypoglycemia and death. A target blood glucose of 8.0-10.0 mmol/L for ICU patients is recom-
mended by the American Diabetes Association.
The NICE-SUGAR Study investigators. Hypoglycemia and risk of death in critically ill patients. NEJM 2012; 367: 110818; Hirsch IB. Understanding
low sugar from NICE-SUGAR. Ibid: 11502 (editorial).
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30 January 2013 Research Reviews
Tiotropium for poorly controlled asthma
Three studies have shown benet from the
addition of tiotropium, a long-acting anti-cholinergic bronchodilator, to inhaled steroid
and long-acting beta-agonist, in the treatment of
poorly controlled asthma. These studies, how-
ever, have only lasted for 8 to 16 weeks and lon-
ger-term studies are needed. Two multinational
48-week replicate studies have been reported
together.
The trials included a total of 912 patients (mean
age 53 years) with asthma poorly controlled on
standard treatment who were randomized to in-
haled tiotropium 5.0 mg or placebo every morn-
ing for 48 weeks. At 24 weeks the mean increase in peak FEV1 from baseline was signicantly
greater in the tiotropium group in both trials (86 mL in trial 1 (n=459 patients) and 154 mL in
trial 2 (n=453). The increase in trough FEV1 was also signicantly greater in the tiotropium
group in both trials. The time to rst severe exacerbation was 282 days (tiotropium) vs 226
days (placebo) and the risk of severe exacerbations was reduced by 21 percent with tiotro-
pium. Adverse events were similar in the two groups.
The addition of tiotropium was benecial for patients with asthma poorly controlled on in-
haled steroid and long-acting beta-agonist.
Kerstjens HAM et al. Tiotropium in asthma poorly controlled with standard combination therapy. NEJM 2012; 367: 1198207; Bel EH. Tiotropium for
asthma promise and caution. Ibid: 12579 (editorial).
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31 January 2013 Research Reviews
Coronary stents for patients with diabetes
There is controversy about the relative merits of various coronary stents for use in patients
with diabetes. Paclitaxel-eluting, sirolimus-eluting, and everolimus-eluting stents haveeach been advocated. A meta-analysis has favored everolimus-eluting stents.
The analysis included 42 trials and 22,844 patient-years of follow-up. All currently useddrug-eluting stents were associated with a decreased risk of target vessel revascularizationamong patients with diabetes compared with bare metal stents. Everolimus-and sirolimus-eluting stents were similar in ecacy and beer than paclitaxel- or zotarolimus-eluting stents.The median target-vessel revascularization rate was 109 per 1000 patient-years with bare met-al stents and 35 per 1000 patient-years with everolimus-eluting stents. There was a 62 percentprobability that everolimus-eluting stents were the safest with the lowest rate of any stent
thrombosis.Among patients with diabetes, drug-eluting stents are more eective than bare-metal stentswithout compromising safety. Everolimus-eluting stents may be the best choice. A BMJedi-torialist questions the cost-eectiveness of drug-eluting stents for patients with diabetes andmaintains that optimal medical treatment will probably remain the core treatment for patientswith diabetes.
Bangalore S et al. Outcomes with various drug eluting or bare metal stents in patients with diabetes mellitus: mixed treatment comparison analysis
of 22,844 patient years of follow-up from randomised trials. BMJ 2012; 345: (Sept 22): 16 (e5170); Mak K-H. Drug eluting stents for patients with
diabetes. Ibid: 7 (e5828) (editorial).
Intra-aortic balloon support after acute
MI: not beneficial
Intra-aortic balloon counterpulsation is widely used for patients with acute myocardialinfarction (MI) and cardiogenic shock and it is recommended in US and European guide-lines, but there is a paucity of good evidence to support its use. Now a multicenter study in
Germany has shown no signicant reduction in 30-day mortality.A total of 600 patients with cardiogenic shock and acute MI who were awaiting early revas-
cularization were randomized to intra-aortic balloon counterpulsation (IABP) or a controlgroup. At 30 days, mortality was 39.7 percent (IABP) vs 41.3 percent (controls), a nonsigni -cant dierence. There were no signicant dierences between the groups in time to hemo-dynamic stabilization, length of stay in intensive care, serum lactate levels, dose or durationof catecholamine therapy, renal function, major bleeding, peripheral ischemic complications,sepsis, or stroke.
Intra-aortic balloon counterpulsation was not signicantly eective.
Thiele H et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. NEJM 2012; 367: 128796; OConnor CM, Rogers JG.
Evidence for overturning the guidelines in cardiogenic shock. Ibid: 134950 (editorial).diabetes. Ibid: 7 (e5828) (editorial).
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32 January 2013 Research Reviews
Blood pressure control in diabetes
It is oen assumed that achieving a low blood pressure is a valid aim for patients at high car-diovascular risk, but data from the UK General Practice Research Database have suggestedthat too low a blood pressure may also be harmful.
Data were analyzed for 126,092 adults with newly diagnosed type 2 diabetes between 1990
and 2005. Almost 10 percent (9.8 percent) of the patients had had a myocardial infarction orstroke before the diagnosis of diabetes. During an average follow-up of 3.5 years, mortality
was 20 percent. Among subjects with cardiovascular disease, blood pressure control to
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33 January 2013 In Pract ice
Introduction
Chronic obstructive pulmonary disease
(COPD) is a chronic disease involving air-ways inammation that aects about 5 per-
cent of the older population.
While cigaree smoking is the biggest
risk factor, long-term exposure to indoor
air pollution caused by burning of biomass
fuels, occupational dust and chemicals and
underdeveloped lungs are among other con-
tributing factors.
Until recently, it was thought that only15 to 20 percent of cigaree smokers would
eventually develop COPD at some stage in
their lives. It is now known that about half
of smokers will develop this debilitating dis-
ease. By 2020, COPD will be the third lead-
ing cause of death worldwide (aer isch-
emic heart disease and stroke) and the sixth
leading cause of disability.
In many countries, COPD exacerbationsare now either the most common or second
most common reason for hospitalization
with an identiable medical condition. The
situation is likely to get worse due to an ag-
ing population. That puts general practice
in an even more important position to diag-
nose the patients before their lung function
deteriorates irreversibly.
COPD is characterized by increased CD8+
T cells and macrophages in biopsies, and in-
creased neutrophils in sputum.
DiagnosisDiagnosis of COPD is a two-step process.
The rst is making a clinical diagnosis. A
GP should suspect COPD if a smoker or ex-
smoker complains of dyspnea, cough, fre-
quent chest infections and chronic sputum
production. But rst, rule out other diseases
including asthma, tuberculosis, congestive
heart failure, obliterative bronchiolitis and
diuse panbronchiolitis using dierentialdiagnosis.
The second part of the diagnosis is equally
as important but happens rather patchily. It
consists of the need to conrm clinical diag-
nosis by performing spirometry lung func-
tion test (LFT). It is a fairly simple procedure
and doesnt cost much. Still, many GPs dont
use it. Thats akin to managing someone
with hypertension without measuring theirblood pressure.
In spirometry, more than 80 percent of the
values of forced expiratory volume in one
second (FEV1), as predicted on the basis of
an individual patients age, sex and ethnicity,
will classify them as having a mild COPD,
whereas 30 to 50 percent of predicted FAV1
indicates severe disease. A FEV1 of less than
30 percent of the predicted value suggests a
very severe COPD.
Managing COPD in primary care
Professor Neil BarnesLondon Chest Hospital,London, UK
Dr. Ong Kian ChungPresident, Singapore COPD Association
Mt Elizabeth Medical Centre, Singapore
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34 January 2013 In Pract ice
While conrming the COPD diagnosis,
the level of lung function also tells you some-
thing about their likelihood of problems in
the future. The worse their lung function,
the more likely they are to run into otherhealth problems in the future.
Practice guidelines
The revised Global initiative for chronic
Obstructive Lung Disease (GOLD) guide-
lines dene two separate aims in COPD
management: symptom reduction and risk
reduction.
The COPD Assessment Test (CAT) is an
8-point unidimensional measure of health sta-
tus impairment. The score ranges from 0 to
40. A score of more than 10 indicates a more
symptomatic patient who should be placed
into B or D groups of the assessment chart.
The 0-4 point modied British Medical
Research Council (mMRC) dyspnea scale
also helps understand the level of breath-
lessness (see Figure).
The assessment of risk can either be done
using the FEV1/FVC (forced vital capacity)
ratio with spirometry, using 1-4 GOLD clas-
sication of airow limitation or it can be
based on the number of exacerbations the
patient has had during the past year. Post
bronchodilator FEV1/FVC of
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35 January 2013 In Pract ice
ance with special aention to administration of
diuretics, anticoagulants, and treatment of co-
morbidities and nutritional deciencies should
be considered.
COPD exacerbations deteriorate qualityof life, reduce lung function that becomes ir-
reversible in many patients, lead to avoidable
hospitalizations and death. Although frequent
exacerbations amount to two or more breath-
ing aacks in a year, each patient needs to be
judged individually. If someone ends up in a
hospital just once with a really bad exacerba-
tion, that should be taken as a red ag from the
risk reduction point of view.
Emphasis on risk reduction is, in fact, the
most important change over the previous
GOLD guidelines. Just as in the management
of ischemic heart disease you want to stop your
patients having angina and chest pain, but also
want to stop them from having a myocardial
infarct. That concept is familiar to most general
practitioners because it is how they approach
the treatment of other chronic diseases.
Compliance
Compliance with drug or non-drug ther-
apies can be a challenge. A good doctor-
patient relationship can, however, help im-
prove compliance. If patients feel that thedoctor has listened to them and that the
treatment addresses their needs, they are
more likely to stick to the drug and non-
drug treatment regimen. A simple drug
regimen also helps. If patients are required
to take multiple medications at different
times of the day, they have more chances
to slip up.
One of the problems with COPD patients
is that they begin to exercise less because
they easily get short of breath. And because
they exercise less, they end up develop-
ing other health problems. Thats why it is
important to recommend physical activity
at an early stage of COPD. The more they
keep themselves active, the better it will be
not just for their COPD symptoms, but also
for other associated chronic diseases.
The aims of COPD management
Reduce symptoms:
Relieve symptoms, improve exercise tolerance, improve health status
Reduce risk:Prevent disease progression, prevent and treat exacerbations, reduce mortality
Online Resources:
GOLD guidelineswww.goldcopd.org
Improving the Dierential Diagnosis of Chronic Obstructive Pulmonary Disease inPrimary Carewww.goo.gl/ZraLr
American Lung Associationwww.lung.org/lung-disease/copd/
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36 January 2013 Calendar
January
16th Bangkok International Symposium
on HIV Medicine16/1/2013 to 18/1/2013
Location: Bangkok, Thailand
Info: Ms. Jeerakan Janhom (Secretariat)
Tel: (66) 2 652 3040 Ext. 102
Fax: (66) 2 254 7574
E-mail: [email protected]
Website: www.hivnat.org/bangkoksymposium
28th Congress o the Asia-Pacifc Academy
o Ophthalmology17/1/2013 to 20/1/2013
Location: Hyderabad, India
Info: APAO Secretariat
Tel: (852) 3943 5827Fax: (852) 2715 9490
Email: [email protected]
Website: www.apaoindia2013.org
Emergency Medicine 201323/1/2013 to 24/1/2013
Location: London, UK
Info: MA Healthcare Conferences (London)Tel: (44) 20 7501 6762Fax: (44) 20 7978 8319
Email: [email protected]
Website: www.mahealthcareevents.co.uk/
4th International Conerence on Legal Medicine,
Medical Negligence and Litigation in Medical
Practice (IAMLE-2013)25/1/2013 to 27/1/2013
Location: Thiruvananthapuram, Kerala, IndiaInfo: Prof. R.K.Sharma, Chairman - IAMLE 2013Tel: (91)11 4158 6401/402Email: [email protected], [email protected]: www.iamleconf.in
FebruaryFood Allergy and Anaphylaxis Meeting (FAAM)
20137/2/2013 to 9/2/2013
Location: Nice, France
Info: EAACI FAAM 2013 Secretariat
Tel: (33) 1 7039 3554
Fax: (33) 1 5385 8283
Email: [email protected]
Website: www.eaaci-faam.org/
International Meeting on Emerging Diseases and
Surveillance (IMED 2013)15/2/2013 to 18/2/2013
Location: Vienna, AustriaInfo: International Society for Infectious Diseases
Tel: (617) 277 0551
Fax: (617) 278 9113
Email: [email protected]
Website: www.isid.org/imed/Index.shtml
Asian Pacifc Society o Cardiology
2013 Congress21/2/2013 to 24/2/2013
Location: Pattaya, Thailand
Info: Kenes Asia (Thailand Office)
Tel: (66) 2 748-7881Fax: (66) 2 748-7880
Email: [email protected]
Website: www2.kenes.com/apsc2013/pages/home.aspx
March
23rd Conerence o the Asia Pacifc Association
or the Study o the Liver7/3/2013 to 10/3/2013
Location: Singapore
Info: Gastroenterological Society of Singapore, The AsianPacific Association for the Study of the Liver
Tel: (65) 6292 4710
Fax: (65) 6292 4721
Email: [email protected]
Website: www.apaslconference.org
62nd American College o Cardiology (ACC)
Annual Scientifc Session9/3/2013 to 11/3/2013
Location: San Francisco, California, US
Info: American College of Cardiology Foundation
Tel: (415) 800 699 5113Email: accreg