Medical Tribune January 2013 ID

7/28/2019 Medical Tribune January 2013 ID

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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


2/42

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.


5/42


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


6/42


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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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


10/42


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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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


12/42


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.


13/42


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-


14/42


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.


15/42


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


16/42


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.


17/42


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


18/42

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


19/42

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.


20/42

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.


21/42


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


22/42


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.


23/42


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.


24/42


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


25/42

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).


26/42


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


27/42


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).


28/42


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


29/42


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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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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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).


32/42


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


33/42

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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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


35/42


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/


36/42

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


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


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


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


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


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

Medical Tribune January 2013 ID

Documents

Transcript of Medical Tribune January 2013 ID