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January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:
January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:
January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:
January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:
January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:

January 2013

January 2013 www.medicaltribune.com New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children:

www.medicaltribune.com

New advisory recommends fewer GERD endoscopies

New advisory recommends fewer GERD endoscopies FORUM SINGAPORE FOCUS TB in children: We need to do
FORUM SINGAPORE FOCUS TB in children: We need to do more World’s first dissolvable drug-eluting
FORUM
SINGAPORE FOCUS
TB in children: We need
to do more
World’s first dissolvable
drug-eluting stent

CONFERENCE

World’s first dissolvable drug-eluting stent CONFERENCE Rapid TB test performs well IN PRACTICE Managing COPD in

Rapid TB test performs well

IN PRACTICE

first dissolvable drug-eluting stent CONFERENCE Rapid TB test performs well IN PRACTICE Managing COPD in primary

Managing COPD in primary care

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January 2013

New advisory recommends fewer GERD endoscopies

Radha Chitale

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 Barrett’s 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 Barrett’s esophagus and early adeno- carcinoma,” the researchers said. But both men and women with a history of Barrett’s 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 reflux 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 committee based their recommenda- tions on a literature review and comparison of 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 first step in most patients with GERD symptoms and is indicated only when empirical PPI therapy for 4-8 weeks is

unsuccessful.”

N ew recommendations for patients with gastroesophageal reflux disease (GERD) advise physicians to avoid

unnecessary endoscopies in patients for whom there is little benefit. Upper endoscopy is a routine procedure for GERD diagnosis and management, particular- ly when monitoring for abnormal or cancerous esophageal tissue, but overuse results in higher healthcare costs and adverse side effects with- out improved patient outcomes. “Limited data suggest that clinicians who care for patients with GERD symptoms often

do not follow suggested practice,” according to the Clinical Guidelines Committee of the American College of Physicians. The Committee 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 often, or are performed before alarm symptoms occur. The best practice recommendations indicate upper endoscopy for patients with heartburn and 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 after 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 Barrett’s

persist with severe esophagitis, or who have a history of a narrowed esophagus. Persistent GERD can
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January 2013

Blood protein resistin reduces statin effect in obese

Rajesh Kumar

C anadian researchers have identified a protein called resistin, secreted by fat

tissue, as the cause of elevated low-density lipoprotein (LDL) in obese people. Their research, presented at the Canadian Cardiovascular Congress recently held in Toronto, 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 efficacy 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, especially those that target and inhibit resistin and

drugs, especially those that target and inhibit resistin and High resistin levels may attenuate the LDL

High resistin levels may attenuate the LDL cholesterol-lowering effects of statins.

thereby increase the effectiveness of statins. Dr. Goh Ping Ping, medical director of the Singapore Heart Foundation, termed the re- search findings as “progressive medical evi- dence” saying they reinforce the importance of treating cholesterol levels to goal in order to 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 healthy

diet.”

Goh. “As physicians, we need to also continuously motivate patients to exercise and adhere to a
Goh. “As physicians, we need to also continuously motivate patients to exercise and adhere to a
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4 Forum January 2013

Forum

January 2013

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.

I t is estimated that 500,000 children become ill with tuberculosis (TB) and that 70,000 af- fected children die annually, but these fig-

ures still do not reflect the true global burden of TB. Childhood TB is an indication of recent transmission, as children tend to acquire the infection in the first year of life, and as such is an indication of household dynamics and epidemiology, especially the emergence of drug resistance in the community. Therefore, TB in children is a litmus test indicating how well we are doing with TB control, and clearly we are failing.

Historical approach The traditional approach to childhood TB has been the assumption that proper iden- tification and treatment of infectious adult cases will prevent childhood TB. But children are not the same as small adults. 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 tuberculosis programs (NTP) because it is difficult to di- agnose with a smear test, it is not usually in- fectious, there are limited resources to tackle TB treatment, and there are a lack of record- ing and reporting approaches. Only about two-thirds of cases are actually notified to NTPs. A cross-sectional study from Indonesia

notified to NTPs. A cross-sectional study from Indonesia A child’s developing immune system makes them susceptible

A child’s developing immune system makes them susceptible to forms of TB.

showed that only 1.6 percent of 4,821 cases of child TB were registered with the NTP there. [BMC Public Health 2011;11:784] Despite available therapies, children have been systematically neglected in a way that has led to preventable morbidity and mortal- ity.

Progress The good news is that for the first time, childhood TB is on the public health agenda, with strong leadership from the WHO and other dedicated groups. Children have been included in guidelines for NTPs and these have been updated in the last several years including reporting prac- tices, dosage revision for young children to avoid hepatotoxicity, and guidance on man- aging TB/HIV co-infections.

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Forum

January 2013

However, despite good policies, imple- mentation can be an issue, especially given looming funding deficits, which affect coun- tries with limited resources in particular. Some methods to combat these barriers would be to integrate families in childhood TB care, including pregnant women and those with HIV infection, in order to con- solidate services. Every clinic visit should be an opportunity to ask about a household TB contact. Empowering healthcare workers at all lev- els to get involved in TB care can yield bet- ter disease reporting statistics. A program in four hospitals in Jakarta, Indonesia, showed that TB diagnosis rates were similar between nurses, general practitioners and pediatri- cians when they received specific training. Pragmatic, simple models of care should be implemented where possible. In one study, directly observed once- weekly treatments for 12 weeks with a com- bination of rifapentine and isoniazid was as effective in adults, if not more, as daily isoniazid-only therapy for 9 months, which could be a better model for treating children. [N Engl J Med 2011;365:2155-2166]

‘‘

Despite available

therapies, children have been

systematically neglected

Partnerships and collaborations with in- dustry could also help improve drug avail- ability and make available new pediatric first-line fixed dose combinations. But for this 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, setting short- to medium- and long-term goals, and being 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 new anti-TB drugs. In children, there was limit- ed evidence for rational TB drug use. There were few rapid diagnostic tests, especially for smear-negative TB and drug-resistant TB, and there were no TB vaccines in human trials. So we really have come a long way, but there are still considerable gaps in TB re- search. Drug formulations tend not to be “child- friendly” – they are unpalatable and difficult to 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 those with drug-resistant TB – more than 80 per- cent of children with multi-drug resistant TB can achieve favorable outcomes, even in the context of HIV positivity. [Clin Infect Dis 2012 Jan 15;54:157-166] However, these regimens are not eas- ily handled. Requiring injections, they work better in older children and some therapies can cause significant hearing loss. More research is required to develop safer multi-drug resistant TB therapy regimes that are shorter and easier to use. No rigorous ev- idence-based management for drug-resistant TB preventive therapy is available for adults, much less for children. Trials to evaluate new therapies and re- gimes should include children and adults.

Diagnostics The challenges in TB diagnosis, which tends to be underfunded, have been a big burden for recognizing TB in the public health framework.

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Forum

January 2013

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 isn’t bacteriologi- cally proven. Children are usually an afterthought 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 better at recog- nizing TB and drug-resistant TB, even in children.

Conclusion Childhood 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 field is mov- ing forward. More progress will require working together in a sustained manner, monitoring progress in order to reach the final goal, which is a generation of children

free of TB.

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7 Singapore Focus January 2013

Singapore Focus

January 2013

New initiatives by Eastern Health Alliance

New initiatives by Eastern Health Alliance A team of nurses, therapists and doctors simulating the resuscitation

A team of nurses, therapists and doctors simulating the resuscitation of a SARS patient with cardiac arrest at SCI, as President Tony Tan and others look on.

S ingapore President Dr. Tony Tan recently launched the Centre for Innovation (CFI) and Changi Simulation Institute (CSI) – two new initiatives by the Eastern Health Alliance to

meet healthcare challenges arising from an ageing population and growth in chronic diseases. The CFI will provide a platform and resources for generating ideas, prototyping them and creating partnerships for healthcare innovations, while CSI will provide relevant medical simulation training for teams of doctors, nurses and allied health professionals. Located alongside Changi General Hospital’s training center, the facilities are open to the members of the alliance and other healthcare partners and will drive healthcare innovation and clinical competencies, respectively.

The alliance will also join A*STAR’s ongoing collaboration with the Center for the In- tegration of Medicine and Innovative Technology (CIMIT) in Boston, Massachusetts, US. This will allow it to benefit from CIMIT’s expertise in developing medical technologies and

solutions, as well as from A*STAR’s science and engineering research capabilities.

developing medical technologies and solutions, as well as from A*STAR’s science and engineering research capabilities.
developing medical technologies and solutions, as well as from A*STAR’s science and engineering research capabilities.
developing medical technologies and solutions, as well as from A*STAR’s science and engineering research capabilities.
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Singapore Focus

January 2013

GSK expands manufacturing capabilities

G laxoSmithKline (GSK) officials detailed plans to continue expanding in Asian markets,

maintaining their operational headquarters in Singapore, during a recent celebration of 40

years of local pharmaceutical manufacturing. “In the last 12 months, we had positive data on 10 new drugs

and we’re going to file for glob-

al approval for six new major medicines before the end of the year,” said GSK CEO Sir Andrew Witty. “Over the next 3 years we should launch about 15 new medications.” Among the drugs in the pipeline will be therapies for HIV, malaria and muscular dystrophy. Witty said Singapore will play a key role in the manufacture of these new drugs, should they be approved for use. Singapore’s Prime Minister Lee Hsien Loong said GSK’s strategy was an important indicator of the value of manufacturing for a large region. “Manufacturing will remain important for [Singapore’s] economy even as it changes,”

he said.

for a large region. “Manufacturing will remain important for [Singapore’s] economy even as it changes,” he
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9 Singapore Focus January 2013

Singapore Focus

January 2013

HPB takes senior citizens ‘back to school’

T o improve health literacy and empower senior citizens to make healthier choices, Singa- pore’s Health Promotion Board (HPB) has developed and piloted a new program in Choa

Chu Kang community. The “Back to School” program incorporates classroom workshops, hands-on and experiential educational activities to help residents and their caregivers understand, for example, the impor- tance of home safety, good oral health and flu vaccination. It also provides senior citizens access

to dental and functional screening services and vaccination for influenza. The program, jointly implemented by HPB and Choa Chu Kang Grassroots Organization and the South View Primary School, will be expanded to more constituencies next year. Minister for Health and MP for Choa Chu Kang GRC, Gan Kim Yong, said the project is in- novative and meaningful and will greatly benefit Choa Chua Kang residents. HPB’s chief executive officer, Ang Hak Seng, said there is a low level of flu vaccine uptake among the elderly, with only one in 10 residents aged 50 to 69 vaccinated in 2011. “The pro- gram not only allows them to be healthy, but to receive flu vaccine and get routine dental

check under one roof.”

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10 Singapore Focus January 2013

Singapore Focus

January 2013

World’s first dissolvable drug-eluting stent

Rajesh Kumar

T he world’s first drug-eluting bioresorb-

able stent promises to revolutionize the

care for patients with coronary artery

disease (CAD). Absorb ® (Abbott Vascular) is made from a naturally dissolvable material called poly- lactide that is commonly used in dissolving

sutures and is coated with the anti-prolifera- tive drug everolimus.

It works by restoring blood flow in the

blocked coronary artery similar to a metal- lic drug-eluting stent but then dissolves into water and carbon dioxide within a few months, leaving behind a treated vessel that may resume its natural elasticity and pulsat- ing movement. The device is being referred to as scaffold rather than stent to indicate its temporary nature and is creating quite a stir amongst interventional cardiologists. “There have been three significant mile- stones in the treatment of CAD in the last

few decades – angioplasty, bare metal stents and drug-eluting stents. The fourth and lat- est revolution has been initiated with the in- troduction of Absorb…it has the potential to transform the way we treat patients,” said Dr. Pieter Cornelis Smits, director of inter- ventional cardiology at Maasstad Zieken- huis in Rotterdam, the Netherlands. “With Absorb, the vessel may return to a more natural state over time, which could provide patients with important clinical ben- efits over the long-term.”

A stent is usually not required after about

6 months of treatment by when the artery gets unblocked and can stay open on its own.

when the artery gets unblocked and can stay open on its own. Absorb, a drug-eluting stent

Absorb, a drug-eluting stent made from polylactide, a naturally dissolvable material.

Some patients may require repeat stenting due to reblockage on either the same or on different sites. As a result, their arterial walls end up becoming rigid in many places due to multiple metal stents left behind, explained Smits.

‘‘

It has the potential

to transform the way we

treat patients

Absorb leaves behind only two pairs of tiny metallic markers which help guide its placement and remain in the artery to enable physician to subsequently see where the de- vice was placed. As a result, the vessel can expand and con- tract as needed to increase the flow of blood to the heart in response to activities such as exercise. The need for long-term treatment with anti-clotting medications may also be reduced and any subsequent interventions would be unobstructed, Smits added. Initial data from multiple ongoing studies in more than 20 countries around the world, including Singapore, indicate that Absorb

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Singapore Focus

January 2013

performs similar to a best-in-class drug-elut- ing stent across traditional measures such as major adverse cardiovascular events and target lesion revascularization, according to Abbott Vascular. Absorb is now available in Europe, the

Middle East, parts of Asia Pacific including Hong Kong, Malaysia and New Zealand, and parts of Latin America. It is not yet regis- tered in Singapore and is currently available through special access route, pending regula-

tory approval by Health Sciences Authority.

pending regula - tory approval by Health Sciences Authority. NUS researchers knock down chikungunya Elvira Manzano

NUS researchers knock down chikungunya

Elvira Manzano

R esearchers from the National Univer- sity of Singapore’s (NUS) Yong Loo Lin

School of Medicine have identified a new gene silencing approach that can kill the chikungunya virus quickly, making prophy- lactic therapy possible for patients with this condition. By employing small hairpin RNA (shR- NA) technology directed against two specific chikungunya virus, E1 and nsP1genes, Ms. Shirley Lam, a postgraduate student from NUS and her team, was able to show that the strategy knocked down the virus and sup- pressed replication in infected cells within 3 days. The approach, tested in both human cells and mice models, was able to protect the cells for up to 15 days, said Lam who received the Singapore Young Scientist Award at the re- cent Singapore Health and Biomedical Con- gress for her work. “Our findings reinforce the potential usefulness of shRNA technol- ogy in clinical settings of chikungunya virus infection.” Chikungunya shares some clinical symp- toms with dengue. “You really need a good diagnostic lab component to come into a play,” said principal investigator Assistant

come into a play,” said principal investigator Assistant Principal investigator Dr. Chu Jang Hann (center), lab

Principal investigator Dr. Chu Jang Hann (center), lab executive Chen Huixin (left) and lead researcher Shirley Lam (right) examine an X-ray film of chikungunya virus protein expression profile.

Professor Justin Hang-Hann Chu, of the De- partment of Microbiology, NUS Yong Loo Lin School of Medicine. “A PCR [polymerase chain reaction] is sensitive enough to tell the difference.” Patients with chikungunya present with a sudden onset of fever, chills, headache, nau- sea and vomiting, joint pain with or without swelling, rash and low back pain. Currently, there is no vaccine or specific treatment for chikungunya infection. Treatment is primar- ily focused at relieving symptoms “which can drag on for months, or even years.” “We have shown that shRNA antiviral technology was effective in inhibiting the

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Singapore Focus

January 2013

virus. It’s even highly specific for chikungu- nya,” Chu said. “We’re looking at it as a pos- sible prophylactic treatment to reduce cases of infection.” Unlike vaccines which provide long-term protection, the approach only gives short- term protection. However, it can be useful during an outbreak, similar to what Singa-

pore experienced between 2008 and 2010 where “we had close to 1,000 chikungunya cases.” The study was funded by the Agency for Science, Technology and Research’s (A*STAR) Biomedical Research Council. Chu’s team is now working to translate their

study results into clinical applications.

to translate their study results into clinical applications. Nine-year-old CKD patient plays scientist Radha Chitale D

Nine-year-old CKD patient plays scientist

Radha Chitale

D espite having chronic kidney disease (CKD) for the majority of her life,

9-year-old Meenakshi Sundaram Losheni has not felt deterred from laboratories. On the contrary, science is her favorite subject and she recently donned a lab coat to join scientists at Singapore’s Institute of Bio- engineering and Nanotechnology (IBN) to participate in their research for a day. “Our researchers are developing next- generation technologies for organ replace- ment and regenerative medicine, and volun- teer opportunities such as this inspire them by putting a face to the biomedical problems that they are working on,” said Professor Jackie Y. Ying, IBN Executive Director. People with CKD progressively and ir- reversibly lose kidney function. As a result, waste builds up in the kidneys, leading to fatigue, low appetite, high blood pressure and nerve and blood vessel damage. Losheni receives hours of dialysis each night, in addi- tion to medication every day. In adults, diabetes and high blood pres-

sure are the primary causes of CKD but chil-

dren may get the disease as a result of a num- ber of afflictions such as obstructive urology and kidney cysts. Children are commonly af- fected between ages 2-5.

‘‘

Volunteer opportunities

such as this inspire

In patients with CKD, progression to end stage renal disease (ESRD) is inevitable and kidney transplants are required. About 70 percent of children with CKD will develop ESRD by age 20; the 10-year survival rate is 80 percent. Death occurs most often due to cardiovascular disease and infection. IBN partnered with the Make-A-Wish Foundation ® Singapore to bring Losheni to their facility in Biopolis. She was able to examine stem cells from liver, bone and kidney that might be used in tissue engineering and present her findings to the lab group. Mr. Paul Heng, board chair of the Make- a-Wish Foundation ® Singapore, said he hoped that the experience, aside from fulfilling Losheni’s intellectual curiosity, would prepare

her for her own kidney transplant.

the experience, aside from fulfilling Losheni’s intellectual curiosity, would prepare her for her own kidney transplant.
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Singapore Focus

January 2013

Bone loss may be an issue after bariatric surgery

Rajesh Kumar

loss may be an issue after bariatric surgery Rajesh Kumar Weight loss is often linked to

Weight loss is often linked to bone loss, with or without surgery

induced changes in hormones that can affect the central regulation of appetite and bone strength. These include the fat-derived hor- mones leptin and adiponectin; gut-derived hormones such as peptide YY (PYY), gluca- gon-like peptide 1 (GLP-1) and ghrelin; and the hypothalamic regulator of energy balance, neuropeptide Y (NPY), the review pointed out. As the number of bariatric operations in- creases, Brzozowska said it was imperative to recognize mechanisms responsible for bar- iatric surgery-induced bone loss, with careful monitoring of bone health including long- term fracture incidence in patients undergo- ing these procedures. Associate Professor Jackie Center, also of the Garvan Institute, said the widely held assump- tion that obese people were protected against bone fragility and fracture was true only up to a point.

S keletal examination before and after bariatric surgery and treatment for po- tential bone loss should form part of pa-

tient care, experts cautioned following review of several research findings suggesting bariat- ric surgery may cause bone loss particularly in young people. In most developed countries, ‘Roux-en-Y’ gastric bypass surgery is the most invasive and commonly used method involving removal of much of the stomach and bypassing of part of the small bowel, while ‘gastric sleeve’ and ‘gastric band’ are the less radical methods of obesity surgery. [Obesity Reviews 2012; DOI:

10.1111/j.1467-789X.2012.01050.x]

“Even though we don’t yet understand all the mechanisms, we can see that the more radical the procedure, the greater the bone loss long-term,” said researcher endocrinol- ogist Dr. Malgorzata Brzozowska of the Gar- van Institute of Medical Research in Sydney, Australia. “In many situations significant weight loss is associated with bone loss, with or without surgery. The more invasive types of surgery appear to heighten bone turnover and the as- sociated bone loss,” she said. “This is thought to be caused not only by rapid weight loss and absorption of fewer vital nutrients like vitamin D and calcium, but possibly also by changes in hormones re- leased by fat and the gut, and their impact on the central nervous system.” Physicians should be aware of surgery-

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Singapore Focus

January 2013

Therefore, on all those undergoing invasive bariatric surgery, “bone mineral densitometry scans can be done and adequate calcium and vitamin D intake advised. For those patients at particular risk, additional monitoring may be advised and protective drugs considered.” Dr. H.G. Baladas of the Raffles Surgery Cen- tre at Raffles Hospital, Singapore said surgeons were well aware of the risks and that’s why bariatric surgery is rarely offered to younger patients who have not yet reached optimum bone growth. Pure bypass operations such as jejunoileal bypass result in the highest bone loss, but are no longer being performed, he said, adding that combined bypass and restriction opera-

tions are associated with a low probability of clinically significant bone loss, but patients with these operations already have their bone mass monitored and take calcium and vitamin D supplements. With the purely restrictive operations such as lap-band and lap sleeve gastrectomy, the risk of bone loss is almost negligible and pa- tients need not routinely take calcium and vi- tamin D supplements, said Baladas. “Studies like these are very important because the number of bariatric operations for morbid obesity is increasing in Asia. In Singapore alone, more than a thousand patients have undergone bariatric surgery for morbid

obesity,” he concluded.

In Singapore alone, more than a thousand patients have undergone bariatric surgery for morbid obesity,” he
In Singapore alone, more than a thousand patients have undergone bariatric surgery for morbid obesity,” he
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16 Singapore Focus January 2013

Singapore Focus

January 2013

Singapore continues to pour funds into biomedical research

Radha Chitale

to pour funds into biomedical research Radha Chitale Over S$100 million in grants have been awarded

Over S$100 million in grants have been awarded to eight biomedical research programs in Singapore.

in Singapore because they are diseases with high-burden and unique presentation among Asian populations. The research program on corneal disease and glaucoma, led by Professor Donald Tan of the Singapore National Eye Centre, and the Singapore Gastric Cancer Consortium, led by Assistant Professor Khay Guan Yeoh at the National University Singapore, were each awarded S$25 million over 5 years. Two more grants, worth S$9 million over 5 years, were given to researchers at the Na- tional Heart Centre Singapore and the Na- tional Cancer Centre Singapore to study heart disease and non-small-cell lung cancer. Another S$58.4 million from Singapore’s Strategic Positioning Fund were awarded to projects within A*STAR. The standout project is the POLARIS (Per- sonalized OMIC Lattice for Advanced Re- search and Improving Stratification) initia- tive, which will receive S$20 million over the next 3 years to improve stratified, or person- alized, medicine by organizing existing local

G rants worth over S$100 million have been awarded to eight biomedical research programs in Singapore that

target important diseases in the Asia-Pacific region. The programs, some new and some ongo- ing, should help Singapore’s biomedical sci- ences sector evolve into a symbiotic web of laboratory research, clinical care and research and industry partnership that will support the country’s bid to turn biomedical sciences into a key economic contributor. “One of Singapore’s key differentiating and competitive value propositions is our ability to integrate our research efforts along the in- novation value chain as well as across mul- tiple research organizations,” said Mr. Lim Chuan Poh, chairman of the Agency for Sci- ence, Technology and Research (A*STAR) and co-chair of the Biomedical Sciences Executive Committee. “We have to make sure that Singapore con- tinually occupies an advantage in this [com- petitive environment] to make sure to con- stantly create high-value jobs in Singapore.” Supported by the National Medical Re- search Council of the Ministry of Health, four Translational and Clinical Research (TCR) Flagship grants totalling S$68 million were awarded to research programs in eye disease, gastric cancer, heart disease and non-small cell lung cancer. Each of these research areas have strong, established scientific and clinical capabilities

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Singapore Focus

January 2013

biomarker research and clinical assays into a pipeline to speed diagnostic and treatment capabilities as well as identify new biomark- ers for potential therapies. “It’s very important that Singapore be seen at the forefront of these developments in [stratified medicine],” said Professor Stephen Smith, vice president (Research) of Nanyang Technological University. Another project seeks to identify larger trends in disease development through close examination of rare disease that are often sin- gle cases, and will receive S$12.7 million over three years. “By understanding the rare, you under- stand the common because you have inroads

into common ailments,” said the Genetic Or- phan Diseases Programme program lead Dr. Bruno Reversade, senior principal investiga- tor at A*STAR’s Institute of Molecular Biology. Two other projects to analyze circulating cancer cells and to develop predictive bio- markers will also each receive S$12.3 million and S$13.4 million, respectively. Key performance indicators, including product development and health outcomes, will be monitored for these projects. “This initiative is adding significantly to Singapore’s GDP [gross domestic product],” said Sir Richard Sykes, chair of the Biomedi- cal Sciences International Advisory Council.

“There has to be some measure of output.”

Council. “There has to be some measure of output.” POLARIS initiative hones in on personalized medicine

POLARIS initiative hones in on personalized medicine

Radha Chitale

A S$20 million initiative by Singaporean research institutes and hospitals to link

biomarker technology and clinical practice could help get specialized therapies to pa- tients who need them. The POLARIS initiative will capitalize on existing genomic and metabolomic research in Singapore, particularly in diseases which have a large burden or a different presenta- tion in Asian populations, based on the prin- ciples of stratified, or personalized, medi- cine. “We want to transform disease manage-

ment by moving away from a one-size-fits- all type of approach to targeting specific

want to transform disease manage- ment by moving away from a one-size-fits- all type of approach
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18 Singapore Focus January 2013

Singapore Focus

January 2013

therapies to specific patient groups,” said program lead Dr. Patrick Tan, of the Genome Institute of Singapore at the Agency for Sci- ence, Technology and Research (A*STAR). “The challenge now lies in how to realize the clinical value of those initial [biomarker] discoveries. In order for that to happen, the technologies that we use to give rise to those discoveries must then be taken from the re- search center back into the clinics where these findings can be implemented in the form of certified clinical tests.” Currently, there is no accredited facility to analyze biomarker assays in Singapore and patient samples must be sent overseas. Tan said they hope to set up a local facil- ity, certified by the College of American Pa- thologists, to carry out standardized, robust testing on routine clinical samples that clini- cians can feel comfortable using to allocate treatment. “At the end of the day, we want the clini- cian to take the information and act on it,” he said. The immediate impact on patients would be validated biomarker assays that quickly identify subgroups of patients who will re- spond to available therapies. However, a portion of patients do not respond to existing therapies. The current model for enrolling such patients in clini- cal trials to receive experimental therapies is time consuming and costly because assess- ing their eligibility is decentralized and re- quires multiple biomarker assays. For exam- ple a cancer patient at the National Cancer Centre Singapore must be evaluated several times to see if they are eligible for one of 40- 50 ongoing clinical trials. During this time, disease can progress, Tan said.

Unresponsive patients who consent to participate in POLARIS would be evaluated once for biomarkers that match existing ex- perimental therapies in ongoing clinical tri- als, which reduces the time it takes for them to receive treatment. Patients who remain unresponsive or who relapse may be evaluated further by whole genome sequencing and other types of bio- marker analysis for novel diagnostic or ther- apeutic targets, to be tested in clinical trials. Pharmaceutical industry involvement to design clinical trials and develop new prod- ucts will be a key facet of POLARIS. “It’s a more orchestrated system to en- hance discoveries and findings based upon patients so that you are capturing the maxi- mum amount of information from each pa- tient with the minimum cost and the most efficiency,” Tan said. Four institutes from A*STAR and clini- cians from Singapore General Hospital, the National Cancer Centre Singapore, Singa- pore National Eye Centre and the National University Health System have partnered to be part of POLARIS. At present, POLARIS will focus on lung and gastric cancers and eye diseases, both because of the heavy local disease burden and because of the number of identified bio- markers. However, the initiative is scalable to other diseases and research groups. POLARIS is funded by a 3-year S$20 mil- lion grant from A*STAR’s Biomedical Re- search Council and represents the integration phase of Singapore’s initiative to grow the

biomedical sciences sector.

initiative to grow the biomedical sciences sector. *Personalized OMIC Lattice for Advanced Research and

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January 2013

43rd Union World Conference on Lung Health, 13-17 November, Kuala Lumpur, Malaysia – Radha Chitale reports

New TB therapies offer hope

T wo promising new agents under de-

velopment for treating multiple drug-

resistant tuberculosis (MDR-TB) can’t

be deployed fast enough, experts say. The US Food and Drug Administration (FDA) Anti-Infective Drugs Advisory Com- mittee has approved a request for accelerated approval of drug-maker Janssen’s 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 five-drug background regimen (standard second-line drugs) for 24 weeks im- proved the rate of sputum culture conversion (shift from positive to negative Mycobacterium 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 effects of bedaquiline were durable out to a follow-up assessment at 72 weeks. Meanwhile, Otsuka Pharmaceuticals Group has filed 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 are frustrated by the prospect of the lengthy up-

take process required to get new therapies to where they are really needed. “Getting [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 differ- 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-

On the ground you’re 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 better definitive evidence of a shorter regimen,” said Dr. Mary Edginton of the University of the Witwatersrand School of Public Health in Johannesburg, South Africa.

tance

“There doesn’t seem to me to be any reason not to use the short course regimens, under

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research conditions, with informed consent of patients, and monitored and reported.” “We’re going to need to pick up the pace,” said Dr. Kenneth Castro, director of the Divi- sion of TB Elimination at the US Centers for Disease 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 year according to the WHO Global Tuberculosis

Report 2012.

year according to the WHO Global Tuberculosis Report 2012. Intense antibiotic therapy may benefit TB meningitis

Intense antibiotic therapy may benefit TB meningitis patients

A n intensified antibiotic treatment regi- men could improve outcomes in patients

with 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 differs from pulmonary tubercu- losis, Ruslami and colleagues have suggested that a higher drug dose may garner better 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, after which they were divided again into groups to receive none, 400 mg, or 800 mg of oral moxifloxacin for 2 weeks, after 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 fluid (CSF), and

penetrate well into the cerebrospinal fluid (CSF), and High-dose IV and oral antibiotics were better than

High-dose IV and oral antibiotics were better than standard therapy in an Indonesian study.

adjunctive corticosteroids. High-dose rifampicin tripled plasma and CSF concentrations compared with those seen with the standard dose (p<0.0001 for both). Patients given 800 mg moxifloxacin had twice the plasma concentration of patients given 400 mg moxifloxacin and a 60 percent increase in CSF concentration (p<0.0001, p=0.006, respectively). “The higher exposure to rifampicin in our study suggests a combination of a higher dose, intravenous administration, and non- linear pharmacokinetics of this antibiotic,”

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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 first 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. Moxifloxa- cin did not appear to affect mortality. “Rifampicin is still an appealing drug for tuberculosis, especially in developing coun- tries since it is cheap, accessible, well toler- ated, and physicians are aware of it,” Ruslami said, adding that defining the optimum regi- men from such drugs could help control TB

meningitis in areas of need.

drugs could help control TB meningitis in areas of need. Rapid TB test performs well onsite

Rapid TB test performs well onsite

L aboratory diagnosis of tuberculosis (TB) improved by 50 percent when a novel

rapid 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 definitive 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 first-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 MSF’s Campaign for Access to Essential Medicines.

“For drug-resistant TB

in high multiple

drug-resistant TB (MDR-TB) settings, you can start patients on an optimized regimen and then send them for a full drug sensitivity test- ing to tailor the regimen.”

Photo credit: WHO
Photo credit: WHO

A new rapid TB diagnostic test has been rolled out in various locations around the world.

MDR-TB diagnosis in low-burden settings still necessitates a confirmatory 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-

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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 number of 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 benefits of the Xpert ® test do not exclude the need for better point of care tests in peripheral, resource-poor settings, 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.

have a simple, fast test that returns good results in TB endemic countries with - out
have a simple, fast test that returns good results in TB endemic countries with - out
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8th International Symposium on Respiratory Diseases and American Thoracic Society in China Forum, 8-11 November, Shanghai, China – Chuah Su Ping reports

Interview with the Presidents

The 8th International Society for Respiratory Disorders (ISRD)

annual meeting marked the inaugural joint scientific 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 Kraft, president of the ATS - to

gain their views on key topics in respiratory diseases.

- to gain their views on key topics in respiratory diseases. Professor Chunxue Bai Dr. Monica

Professor

Chunxue Bai

on key topics in respiratory diseases. Professor Chunxue Bai Dr. Monica Kraft MT: How will the

Dr. Monica Kraft

MT: How will the updated Global Initia- tive for COPD (GOLD) guidelines affect current clinical practice? Kraft: The main difference is the criteria for diagnoses [of COPD]. They’re quite different from previous versions and we are current- ly in an adjustment period trying to better understand how to best apply these guide- lines in practice. The definitions of different 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 doctor’s office. 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 is very useful in the diagnosis and treatment of sleep apnea. Kraft: I think telemedicine is still an evolv- ing field, 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-

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small-cell lung cancer (NSCLC)]. However, at the end of the day, early diagnosis of lung cancer is key to extending patient survival. Kraft: Lung cancer remains a very challeng- ing area, but I think we’ve made some prog- ress in recent years. It’s exciting that we have discovered specific biomarkers and patterns

of gene expression which are associated with response to specific chemo-therapeutic agents, as this can help us ensure patients are receiving the right combination of medi- cation. In other words we are getting closer to the goal of personalized therapy in lung

cancer.

closer to the goal of personalized therapy in lung cancer. Towards targeted COPD treatment C hronic

Towards targeted COPD treatment

C hronic obstructive pulmonary disease (COPD) treatment should be individual-

ized based on each patient’s 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. George’s, 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 benefit and risk reduction, said Jones, who is a member of the GOLD Science Committee. Symptomatic benefit includes relief of symp- toms, improvement in exercise tolerance and health status whereas risk reduction includes prevention 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 differ 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, approximately 70 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 year’s GOLD [2012] update, we also recognize that hospitalization is a very important risk factor. If a patient has had one 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 efficacy correlated with changes in the St. George’s Respiratory Ques- tionnaire (SGRQ) score. “If the patients judged their treatment as ‘ineffective’, that correlated with a worse SGRQ score. However, if they judged their treatment as ‘effective‘ or ‘very effective’, the improvement in SGRQ score was either at the threshold of clinical significance or bet- ter,” said Jones. [Am J Respir Crit Care Med

1997;155:1283-1289]

“These findings are significant 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 significantly greater change in symptoms compared with patients on tiotropium alone. “These results are in line with the COPD guideline recom- mendations to combine bronchodilators with different 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- tient’s symptoms and reduce exacerbations,” Jones said. Physicians can then custom- ize treatment based on the patient’s clinical

phenotype.

ize treatment based on the patient’s clinical phenotype. NIPPV for treating COPD exacerbations N on-invasive

NIPPV for treating COPD exacerbations

N on-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 first of all reduce the patient’s breathing workload,” 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 will eventually determine treatment success in patients with COPD exacerbations.” But he noted that patient collaboration and the skill of hospital staff can play a ma- jor role in how effective 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 significant 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 a need 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 benefit sig- nificantly from ventilator assistance. “NIPPV has been shown to reduce the se- verity of breathlessness within the first 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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tions. “NIPPV preserves the patient’s 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 settings but it is impor- tant to take into consideration the patient’s personal feedback as well as the need for fully trained and experienced hospital staff and appropriate equipment, monitoring and

support.”

staff and appropriate equipment, monitoring and support.” OSA linked to glucose dysmetabolism A ccumulating evidence

OSA linked to glucose dysmetabolism

A ccumulating 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 that severe 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,

glucose me - tabolism including impaired fasting glucose, CPAP has been shown to improve insulin sensitivity

CPAP has been shown to improve insulin sensitivity in non-diabetic patients.

impaired glucose tolerance and occult diabe- tes. [Diabetes Care 2008;31:1001-1007]

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“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/m 2 . [Am J Respir Crit Care Med 2004;169:152-62] However, the effects of CPAP treatment in patients with T2DM remains controversial, Ip said.

“Many studies have been carried out to ex- amine the effect of CPAP treatment of OSA in patients with T2DM, however, most did not report any significant difference 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, little is known about the long-term outcomes of OSA treatment for T2DM, which Ip said would be a key area for

future research.

T2DM, which Ip said would be a key area for future research. CPAP may improve cognitive

CPAP may improve cognitive function in OSA patients

C ontinuous positive airway pressure (CPAP) treatment for obstructive sleep

apnea (OSA) may improve neurocognitive function, show the latest results from the Apnea Positive Pressure Long-Term Efficacy Study (APPLES). “Up till recently, there have been studies examining the effect 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 batteries 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 specific deficits in neurocognitive function in a large heterogenous population of OSA patients and to assess the long-term effec- tiveness of CPAP therapy on neurocognition, mood, sleepiness and quality of life. It also sought to evaluate which deficits are revers- ible and most sensitive to the effects of CPAP. [J Clin Sleep Med 2006;2:288-300] The primary outcomes examined were attention and psychomotor function; learn- ing and memory (L/M); and executive and

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frontal-lobe function (E/F). “These were ex- amined via the Pathfinder Number (PN) Test, the Buschke Selective Reminding Test (BSRT), and the Sustained Working Memory Test (SWMT), respectively,” said Kushida, who is also president of the World Sleep Federation. “While covariate-adjusted analyses re- vealed no significant differences in the PN and BSRT test results between the active CPAP and sham group, we did find signifi- cantly better SWMT results, which examined E/F, in the active CPAP group,” he said. Low- er levels of oxygen saturation and increased sleepiness also produced significant effects on the E/F test. “However, these effects were only de- tected at 2 months and were minor com- pared with the effects of caffeine and diphenhydramine for this measure in other studies,” he noted. Interestingly, the study also reported that adherence to CPAP was significantly lower in the sham group, and this, said Kushida, was a major limitation in APPLES.

Interpreting APPLES “The detection of CPAP effects in the pri- mary E/F variable suggests that the SWMT test - in which a cognitive task is combined with simultaneous electroencephalographic measures 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 effect on CPAP on neuro- cognition in APPLES, suggest the existence of a complex OSA-neurocognitive relation- ship. Clinicians should consider disease severity, sleepiness, individual differences (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 efficacy or in- efficacy of CPAP therapy on this very preva- lent sleep-related breathing disorder.” The results of APPLES are expected to be

published in December 2013.

of APPLES are expected to be published in December 2013. READ JPOG ANYTIME, ANYWHERE. Download the

READ JPOG ANYTIME, ANYWHERE.

Download the digital edition today at www.jpog.com

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Personal Perspectives

Personal Perspectives ‘‘ In developing the new GOLD guidelines, we set clear treatment objectives based on

‘‘

In developing the new GOLD guidelines, we set clear treatment objectives based on improving symptoms; and for the first 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

of exacerbations. Paul W. Jones, University of London, UK ‘‘ One of the things we need
of exacerbations. Paul W. Jones, University of London, UK ‘‘ One of the things we need

‘‘

One of the things we need to do is to strengthen the bridge between Eastern 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 first of all reflect the prevalence of the disorders in the [host] country. Sleep apnea, lung cancer and COPD are all prevalent in China. Second, it should also reflect the emerging science which will affect treatment and diagnosis. Third, it should support ongoing research within the country. Lastly, it should also define 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.

Teofilo Lee-Chiong, University of Colorado, US

together. Teofilo Lee-Chiong, University of Colorado, US ‘‘ Being an international conference with delegates

‘‘

Being an international conference with delegates attending from all over the world, there should be more English speaking staff on hand. Every time we need any help, we have to go the secretariat office. Other than that, everything else was great.

Maulik Sanghvi, India

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31 Gastroesophageal Reflux Disease January 2013

Gastroesophageal Reflux Disease

January 2013

Once weekly exercise enough to reduce GERD risk in obese

Rajesh Kumar

pared with low physical activity (adjusted hazard ratio [HR] 0.41). Among the 2,146 normal-weight participants, a decreased risk of GERD was seen with higher physical ac- tivity (HR 0.59), but the benefit was negated after adjusting for potential cofounders such as sleeping problems and high comorbidity. A similar trend was seen in 1,859 overweight participants. The study’s 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, BMI and possible previous surgical interventions for GERD, said the study authors. Because it is a cross-sectional study, it is not possible to know if the participants with a self-detected association between reflux and physical exercise may have changed their behavior, resulting in reverse causality, they said. The current findings confirm the previous population-based studies assessing an asso- ciation between physical activity and GERD within the general population. “However, none of the previous studies stratified analyses for BMI categories; mean- ing that the decreased risk of GERD limited to obese individuals is a first time observation,” said authors Dr. Therese Djärv and colleagues at the department of molecular medicine and surgery, Karolinska Institutet in Stockholm, Sweden. Should the present results be confirmed in future research, the findings from this study might be important for the prevention and treatment of GERD and its complications,

they concluded.

O bese individuals can reduce their

risk of developing gastroesophageal

reflux disease (GERD) by exercis-

ing even if only once-a-week, according to a

Swedish study. However, no such benefit 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 the Swedish registry of the total population for

a cross-sectional survey. Data on their physi-

cal activity, GERD, BMI and the covariates age, gender, comorbidity, education, sleep- ing problems, and tobacco smoking were ob- tained using validated questionnaires. GERD was self-reported and defined as heartburn or regurgitation at least once weekly, and the presence of at least moderate problems from such symptoms. Frequency of physical activity was categorized into high (several times/week), intermediate (approxi- mately once weekly) and low (1-3 times a month or less). Analyses were stratified for participants with normal weight (BMI < 25 kg/m 2 ), over-

weight (BMI 25 to ≤ 30 kg/m 2 ) and obese (BMI

> 30 kg/m 2 ). Obese participants were on aver-

age slightly older, had fewer years of educa- tion, more comorbidity, slightly more sleeping problems, lower frequency of physical activity, and higher occurrence of GERD. In 680 obese individuals, intermediate fre- quency of physical activity was associated with a decreased occurrence of GERD com-

individuals, intermediate fre - quency of physical activity was associated with a decreased occurrence of GERD
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32 Gastroesophageal Reflux Disease January 2013

Gastroesophageal Reflux Disease

January 2013

Barrett’s esophagus linked to type 2 diabetes

Alexandra Kirsten

esophagus linked to type 2 diabetes Alexandra Kirsten Patients with Barrett’s esophagus were also more likely

Patients with Barrett’s esophagus were also more likely to have smoked or consumed alcohol, and had a higher mean BMI than controls.

“Interestingly, we found that among the study cohort, if you had diabetes there was a twofold increase in your risk for Barrett’s esophagus,” Iyer said. “When we stratified the results by gender, the association of type 2 diabetes with Barrett’s esophagus was stron- ger in males compared to females, which may reflect the different fat distributions in men and women.” There is some evidence that central obe- sity is a risk factor for Barrett’s esophagus and esophageal cancer through mechanical or metabolic mechanisms, such as hyperin- sulinemia. The researchers suggested fat in the abdomen could be a reflux-independent mechanism leading to Barrett’s esophagus which is known to be a precursor of esopha- geal adenocarcinoma. ”If we find the precursor early enough, we could put these patients under surveillance or treat the precursor and reduce the risk,” Iyer said. He added that further prospective studies are needed to better understand the link between Barrett’s esophagus and type 2

diabetes.

the link between Barrett’s esophagus and type 2 diabetes. A retrospective study has shown that patients

A retrospective study has shown that

patients with type 2 diabetes have

twice the risk of Barrett’s esopha-

gus, a condition where the esophageal lin- ing becomes abnormal, whether or not other risk factors such as smoking or obesity were present. The findings were presented during the American College of Gastroenterology’s 77th Annual Scientific Meeting, held recently in Las Vegas, Nevada, US. [Abstract 49] To determine whether there is an asso- ciation between type 2 diabetes and Barrett’s esophagus, 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 researchers conducted a population-based, case-control study. They identified 14,245 patients with Bar- rett’s esophagus and 70,361 control subjects who were matched for age, sex, enrolment date, duration of follow-up, and practice re- gion using the United Kingdom’s General Practice Research Database, a primary care database that includes over 8 million patients. The data showed that patients with Bar- rett’s esophagus were more likely to have smoked and consumed alcohol, had a higher body mass index, and a higher prevalence of type 2 diabetes than control subjects. Multivariate analysis showed a 49 per- cent increased risk for Barrett’s esophagus in patients 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).

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33 News January 2013

News

January 2013

Health impact of open-fire cooking to be studied

Alexandra Kirsten

impact of open-fire cooking to be studied Alexandra Kirsten The large-scale study will also assess the

The large-scale study will also assess the potential of low-emission cook stoves to reduce disease.

“Given that an estimated 3 billion people worldwide are cooking over fire and smoke, we need to better understand how these pol- lutants are affecting public health as well as regional air quality and even the climate,” said Wiedinmyer. The research group will focus on deter- mining the influence 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 efficient stoves positively affect regional air quality. Surveys among vil- lagers on their understanding of the connec- tion between open-fire 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-fire emissions are affecting weather patterns that

contribute to global warming.

weather patterns that contribute to global warming. T oxic smoke and soot from open- fire cooking

T oxic smoke and soot from open- fire cooking causes nearly 2 million deaths each year, primarily among

women and children who spend the most time at fireside, 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-fire cook- ing on regional air quality and disease. “Pollutants and particles spewed by open fires 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 first to discuss broad- scale solutions to disease and pollution from open-fire 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 effects of smoke from traditional cooking methods on households, villages, and entire regions.

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34 News January 2013

News

January 2013

Elderly face higher hip fracture risk after starting BP drugs

Rajesh Kumar

for ACE inhibitors (IRR, 1.53, 95% CI, 1.12 to 2.10) and β-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 first dose hypotension, especially in pa- tients who are already on diuretics. But it is not clear why β-blockers were also implicated in the study. “Elderly patients are more likely to have sick sinus syndrome and β-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 effect of anti- hypertensive medications more marked in them, he said, adding that physicians should start with the lowest possible dose of one medication and first check for postural hy- potension, particularly when starting ACE inhibitors and β-blockers in elderly patients. “Check the heart rate before starting β-blockers…and educate the patient to get up slowly out of the bed or chair. Wait for any giddiness or instability to subside before taking 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 too

low, he concluded.

E lderly hypertensive patients may be at higher risk of hip fractures in the first 45 days after 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 first 45 days following therapy initia- tion, with equal control periods before and after that and a total of 450-day observation

period.[ArchInternMed2012;doi:10.1001/2013.

jamainternmed.469]

The outcome was the first 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% confi- 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 channel blockers in the elderly is already associated with an immediate increased risk of falls. The study sought to find 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 significance only

for all classes of antihypertensive drugs (IRRs, 1.30 to 1.58), al - though it reached statistical
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35 News January 2013

News

January 2013

CABG more effective than PCI in older CAD patients

Rajesh Kumar

more effective than PCI in older CAD patients Rajesh Kumar Researchers analyzed pooled data from 10

Researchers analyzed pooled data from 10 clinical trials involving patients who had undergone CABG or PCI.

Dr. Kenneth Ng Kwan Chung, cardiologist at Novena Heart Centre in Singapore, said in- creasing age is known to be a risk factor for mortality and complications resulting from CABG. “Therefore in patients who are elderly, we sometimes attempt to perform PCI on the ste- notic lesions rather than send them for surgery. However, this study points out that the older patients actually benefit more from CABG than PCI. It could be that older patients have more diffuse disease than younger patients.” Ng said the findings are relevant forAsians as we have a higher proportion of patients who are diabetic, compared with Caucasians, and have a 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 could be a better option than PCI if they have triple vessel disease and diabetes. This is because of a 21 percent lower risk of cardiovascular mortality in the >65 years age group in the study,” he said. “Also, there was no difference in compli- cations between the PCI and CABG groups in terms of death from the procedure and

stroke.”

groups in terms of death from the procedure and stroke.” I n patients with multivessel coronary

I n patients with multivessel coronary ar-

tery disease, coronary artery bypass graft

(CABG) surgery was more effective in an

older cohort, while percutaneous coronary intervention (PCI) was favored in a relatively younger one in a large analysis. Researchers pooled individual data from 7,812 patients who were randomized in 10 clinical trials of CABG or PCI to assess whether patient age modifies the comparative effective- ness of those interventions. [J Am Coll Cardiol 2012; 60:2150-2157] They analyzed age as a continuous vari- able in the primary analysis and divided it into three groups of ≤56.2 years, 56.3 to 65.1 years and ≥65.2 years for descriptive purposes. The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up and angina at 1 year. Old- er patients were more likely to have hyperten- sion, diabetes, and 3-vessel disease compared with younger patients (p=0.001 for trend). Over a median follow-up of 5.9 years, the effect 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 confidence intervals of 1.23 (95% CI 0.95 to 1.59) in the youngest group; 0.89 (95% CI 0.73 to 1.10) in the middle group; and 0.79 (95% CI 0.67 to 0.94) in the oldest group. The CABG/PCI hazard ratio was less than 1 for patients ≥59 years. A similar interaction of age with treatment was present for the compos- ite outcome of death or myocardial infarction. In contrast, patient age did not alter the com- parative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina.

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36 News January 2013

News

January 2013

Bleeding rates with warfarin much higher in reality?

Elvira Manzano

T he rates of major bleeding with warfa-

rin use in atrial fibrillation (AF) may be

higher than reported in clinical trials

and are often fatal, new research suggests. A population-based study conducted in Canada involving 125,195 patients who start- ed warfarin therapy after a diagnosis of AF showed 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- fined as a visit to an emergency department or admission to hospital) was highest during the first 30 days of treatment (11.8 percent per person-year). [CMAJ 2012;doi:10.1503/

cmaj.121218]

The results were important as they re- flect 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 difference, she said, may be due to the strict inclusion criteria and close monitoring of 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-estimates of bleeding rates among patients on warfarin.

of bleeding rates among patients on warfarin. Real-life bleeding rates associated with warfarin may be

Real-life bleeding rates associated with warfarin may be much higher than those reported in clinical trials.

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 at

5 years. In total, 1,963 patients (18.1 percent) died in the hospital or a week after 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 shift to new oral anticoagulants could not be made

on the basis of these data alone, she said.

However, the decision to shift to new oral anticoagulants could not be made on the basis
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38 News January 2013

News

January 2013

Digoxin linked to raised mortality risk in patients with AF

Rajesh Kumar

P hysicians should reassess the role of di-

goxin in the management of atrial fibril-

lation (AF) in patients with or without

heart failure (HF), experts warned following study findings that link the drug to “a signifi- 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 J 2012; 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% confidence interval

(CI), 1.19 to 1.67, p<0.001], 35 percent increase in cardiovascular mortality (EHR, 1.35, 95% CI,

1.06 to 1.71, p=0.016), and 61 percent increase

in arrhythmic mortality (EHR, 1.61, 95% CI,

1.12 to 2.30, p=0.009). The all-cause mortality

was increased in patients with or without HF (EHR, 1.37, 95% CI, 1.05 to 1.79, p=0.019 and EHR 1.41, 95% CI 1.09 to 1.84, p=0.010, respec- tively). The higher mortality remained even after controlling for other medications and risk factors, and regardless of gender.

alternatives to digoxin as a first-line, such as β-blockers or calcium channel blockers, said co-researcher Dr. Samy Claude Elayi, associ- ate professor of medicine at the Gill Heart In- stitute, University of Kentucky in Lexington, Kentucky, US. And if digoxin is used, use a low dose with careful clinical follow-up, eval- uate potential drug interactions when starting new medications, and monitor plasma digox- in levels, added Elayi. “Patients should be aware of potential tox- icity and see their physicians immediately in specific clinical situations, for instance if they experience palpitations or syncope, as those may precede arrhythmic death,” he cautioned. Until now, there have been limited data on the use of digoxin in AF patients as it has scarcely been studied in these patients. The main prospective randomized controlled tri- als involving the drug were performed in pa- tients with HF and sinus rhythm, excluding those with AF, said the researchers. The mechanism by which the drug increas- es deaths among patients is unclear. Mortality from classic cardiovascular causes, whether due to arrhythmia or not, can partly but not entirely explain it. This suggests there must be some additional mechanism that remains to be identified, they added. “There is a need for further studies of the drug’s use, particularly in systolic HF and AF – patients that would, in theory, benefit the most

from digoxin,” concluded Elayi.

theory, benefit the most from digoxin,” concluded Elayi. In view of these findings, we should try

In view of these findings, we should try to control a patient’s heart rate by using

*AFFIRM:

Atrial

Fibrillation

Follow-up

Investigation

of

Rhythm

Management

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39 Research Reviews January 2013

Research Reviews

January 2013

Devices to remove thrombus in acute ischemic stroke

T reatments for acute ischemic stroke include use of IV recombinant tissue plasminogen ac-

tivator (rt-PA), intra-arterial fibrinolysis 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 flexible nitinol wire with distal corkscrew-shaped coil loops with attached filaments. 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.

percent, and 90-day mortality was 17 percent vs 38 percent. The Trevo and Solitaire devices were

The Trevo and Solitaire devices were both better 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: 1231–40; Saver JL et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised parallel-group, non-inferiority trial. Ibid: 1241–9; Gorelick PB. Assessment of stent retrievers in acute ischaemic stroke. Ibid: 1208–10 (comment).

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40 Research Reviews January 2013

Research Reviews

January 2013

Predicting CV risk with C-reactive protein, fibrinogen levels T here is debate about the usefulness
Predicting CV risk with C-reactive
protein, fibrinogen levels
T here is debate about the usefulness of measuring C-reactive protein and fibrinogen levels
in healthy people to predict risk of cardiovascular disease. An analysis of 52 prospective
studies (n=246,669 participants) without known cardiovascular disease has been reported.
It was estimated that the addition of C-reactive protein or fibrinogen to standard risk factors
would improve the classification 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 fibrinogen 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 fibrinogen 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, fibrinogen, and cardiovascular disease prediction. NEJM 2012; 367: 1310–20.

Prasugrel vs clopidogrel for ACS without revascularization

T here is uncertainty about optimum platelet inhibition therapy for patients with unstable angina 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 <75 years were randomized to take either prasugrel 10 mg daily or clopidogrel 75 mg daily, in addition to aspirin, for up to 30 months. After an average follow-up of 17 months the primary end-point (cardiovascular death, myocardial infarction or stroke) was reached by 13.9 percent (prasugrel) vs 16.0 percent (clopidogrel), a nonsignificant difference. Further analysis of multiple ischemic events suggested a lower risk with prasugrel (a significant 15 percent reduction). Heart failure was more frequent in the clopidogrel group. Otherwise, the rate of adverse events was similar in the two groups. Prasugrel did not reduce the frequency of the primary endpoint significantly compared with

clopidogrel.

primary endpoint significantly compared with clopidogrel. Roe MT et al. Prasugrel versus clopidogrel for acute

Roe MT et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularisation. NEJM 2012; 367: 1297–309.

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Research Reviews

January 2013

Perioperative and anesthetic-related deaths: Systematic review, meta-analysis

A systematic review and meta-analysis has assessed changes in perioperative mortality in developed 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 the 1970s, 52 per million in the 1970s and 80s, and 34 per million in the 1990s and 2000s. The cor- responding figures 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 significant relationship between HDI score and perioperative and anesthetic-re- lated mortality. Rates of anesthetic-related mortality fell significantly in high-HDI (developed) countries but rose in low-HDI (developing) countries. Total perioperative mortality decreased

in both high and low HDI countries but the decrease was slower in low HDI countries. Rates of 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 significantly over the last few decades but the decrease has been slower in developing countries. More attention needs to be given to increasing evidence-based

best practice in developing countries.

evidence-based best practice in developing countries. Bainbridge D et al. Perioperative and anaesthetic-related

Bainbridge D et al. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet 2012; 380: 1075–81; Avidan MS, Kheterpal S. Perioperative mortality in developed and developing countries. Ibid: 1038–9 (comment).

Tranexamic acid and death from traumatic bleeding T ranexamic acid given within 3 hours of
Tranexamic acid and death from
traumatic bleeding
T ranexamic 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 the
benefit 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 hours
of injury and stratified according to risk of death at baseline (<6 percent, 6-20 percent, 21-50
percent, or >50 percent). In these risk strata, the reduction in risk of death with tranexamic
acid was 37, 29, 32 and 28 percent, respectively, with no significant difference 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 all
degrees of severity of injury.
Roberts I et al. Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial.
BMJ 2012; 345 (Oct 6): 16 (e5839).
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Research Reviews

January 2013

MRI abnormalities in radiologically normal knees

M any people with knee pain have no abnor- mality on knee X-rays. A US study has shown

that MRI in these circumstances may show abnor- malities of questionable clinical significance. 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 after the age of 50 whether or not the subject com- plains of knee pain and are therefore of question- able clinical significance.

and are therefore of question - able clinical significance. Guermazi A et al. Prevalence of abnormalities

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).

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Research Reviews

January 2013

Hyperglycemia and hypoglycemia in critically ill patients

S evere hyperglycemia in patients in the inten- sive care unit (ICU) is associated with increased

mortality. Initial reports suggested that careful control of blood glucose levels might reduce this mortality but these findings have not been con- firmed 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 2.3–3.9 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 in patients 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.

is recom - mended by the American Diabetes Association. The NICE-SUGAR Study investigators. Hypoglycemia and risk
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Research Reviews

January 2013

Tiotropium for poorly controlled asthma

T hree studies have shown benefit 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 significantly 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 significantly greater in the tiotropium group in both trials. The time to first 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 beneficial for patients with asthma poorly controlled on in-

haled steroid and long-acting beta-agonist.

on in - haled steroid and long-acting beta-agonist. Kerstjens HAM et al. Tiotropium in asthma poorly

Kerstjens HAM et al. Tiotropium in asthma poorly controlled with standard combination therapy. NEJM 2012; 367: 1198–207; Bel EH. Tiotropium for asthma – promise and caution. Ibid: 1257–9 (editorial).

therapy. NEJM 2012; 367: 1198–207; Bel EH. Tiotropium for asthma – promise and caution. Ibid: 1257–9
45
45
45 Research Reviews January 2013

Research Reviews

January 2013

Coronary stents for patients with diabetes T here is controversy about the relative merits of
Coronary stents for patients with diabetes
T here is controversy about the relative merits of various coronary stents for use in patients
with diabetes. Paclitaxel-eluting, sirolimus-eluting, and everolimus-eluting stents have
each 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 used
drug-eluting stents were associated with a decreased risk of target vessel revascularization
among patients with diabetes compared with bare metal stents. Everolimus-and sirolimus-
eluting stents were similar in efficacy and better 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 percent
probability that everolimus-eluting stents were the safest with the lowest rate of ‘any’ stent
thrombosis.
Among patients with diabetes, drug-eluting stents are more effective than bare-metal stents
without compromising safety. Everolimus-eluting stents may be the best choice. A BMJ edi-
torialist questions the cost-effectiveness of drug-eluting stents for patients with diabetes and
maintains that optimal medical treatment will probably remain the core treatment for patients
with 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 I ntra-aortic balloon counterpulsation is widely used
Intra-aortic balloon support after acute
MI: not beneficial
I ntra-aortic balloon counterpulsation is widely used for patients with acute myocardial
infarction (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 significant 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 control
group. At 30 days, mortality was 39.7 percent (IABP) vs 41.3 percent (controls), a nonsignifi-
cant difference. There were no significant differences between the groups in time to hemo-
dynamic stabilization, length of stay in intensive care, serum lactate levels, dose or duration
of catecholamine therapy, renal function, major bleeding, peripheral ischemic complications,
sepsis, or stroke.
Intra-aortic balloon counterpulsation was not significantly effective.
Thiele H et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. NEJM 2012; 367: 1287–96; O’Connor CM, Rogers JG.
Evidence for overturning the guidelines in cardiogenic shock. Ibid: 1349–50 (editorial).diabetes. Ibid: 7 (e5828) (editorial).
46
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46 Research Reviews January 2013

Research Reviews

January 2013

Blood pressure control in diabetes

Reviews January 2013 Blood pressure control in diabetes I t is often assumed that achieving a

I t is often 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 suggested that 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 or stroke 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 <130/80 mmHg did not reduce mortality after adjustment for risk factors. Patients with systolic blood pressure maintained at 110 mmHg had a 2.8-fold increase in mortality compared with pa- tients whose systolic blood pressure was maintained at 130–139 mmHg. For diastolic blood pressure there were significant increases in all-cause mortality of 32 percent with pressures of 70–74 mmHg, and 89 percent with pressures of <70 mmHg, compared with pressures of 80–84 mmHg. The findings were similar for patients without known cardiovascular disease. Among patients with newly diagnosed type 2 diabetes, too strict a control of blood pressure

may be hazardous.

Vamos EP et al. Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study. BMJ 2012; 345 (Sept 22): 18 (e5567).

mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study. BMJ 2012; 345 (Sept
mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study. BMJ 2012; 345 (Sept
47
47
47 In Practice January 2013

In Practice

January 2013

Managing COPD in primary care

Professor Neil Barnes London Chest Hospital, London, UK

Professor Neil Barnes

London Chest Hospital, London, UK

Introduction Chronic obstructive pulmonary disease (COPD) is a chronic disease involving air- ways inflammation that affects about 5 per- cent of the older population. While cigarette 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 only 15 to 20 percent of cigarette 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 (after isch- emic heart disease and stroke) and the sixth leading cause of disability. In many countries, COPD exacerbations are now either the most common or second most common reason for hospitalization with an identifiable 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-

Dr. Ong Kian Chung President, Singapore COPD Association Mt Elizabeth Medical Centre, Singapore

Dr. Ong Kian Chung

President, Singapore COPD Association Mt Elizabeth Medical Centre, Singapore

creased neutrophils in sputum.

Diagnosis Diagnosis of COPD is a two-step process. The first 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 first, rule out other diseases including asthma, tuberculosis, congestive heart failure, obliterative bronchiolitis and diffuse panbronchiolitis using differential diagnosis. The second part of the diagnosis is equally as important but happens rather patchily. It consists of the need to confirm clinical diag- nosis by performing spirometry lung func- tion test (LFT). It is a fairly simple procedure and doesn’t cost much. Still, many GPs don’t use it. That’s akin to managing someone with hypertension without measuring their blood 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 patient’s 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.

48
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48 In Practice January 2013

In Practice

January 2013

While confirming 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 other health problems in the future.

Practice guidelines The revised “Global initiative for chronic Obstructive Lung Disease (GOLD)” guide- lines define 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 modified 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- sification of airflow limitation or it can be based on the number of exacerbations the patient has had during the past year. Post bronchodilator FEV1/FVC of <0.70 confirms

Figure: Assessment of COPD

Risk (Gold Classification of Airflow Limitation)

(Exacerbation history)

Risk

4

   
 

3

(C)

(D)

2

   

1

(A)

(B)

 

mMRC 0-1

mMRC 2

CAT <10

CAT 10

Symptoms (mMRC or CAT score)

2 or

more

Less

than 2

Symptoms (mMRC or CAT score) 2 or more Less than 2 The two main aims of

The two main aims of COPD management should be to reduce a patient’s symptoms and their risk of disease progression.

persistent airflow limitation. Patients with a history of 2 or more exacerbations per year or very severe airflow limitation belong to the high risk groups C or D.

Treatment Treatment strategy for COPD is similar to ischemic heart disease as it uses a range of different drug and non-drug therapies such as smoking cessation, lifestyle changes, flu vaccination to help prevent chest infections, pulmonary rehabilitation, and drug therapy. The latter includes short and long acting β2- agonists (SABA/LABA) and muscarinic an- tagonists (SAMA/LAMA), inhaled cortico- steroids (ICS), phosphodiesterase-4 (PDE-4) inhibitors and long-acting anticholinergics such as tiotropium that are commonly recom- mended in varying combinations, depending on the disease severity. Patients with COPD are at high risk of de- veloping other comorbidities such as cardio- vascular disease, osteoporosis, depression and anxiety, skeletal muscle dysfunction, metabolic syndrome and lung cancer that can have a sig- nificant impact on their prognosis. Depending on their clinical condition, the GOLD guide- lines recommend that an appropriate fluid bal-

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49 In Practice January 2013

In Practice

January 2013

ance with special attention to administration of diuretics, anticoagulants, and treatment of co- morbidities and nutritional deficiencies should be considered. COPD exacerbations deteriorate quality of 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 attacks 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 flag 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 the doctor 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. That’s 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.

symptoms, but also for other associated chronic diseases. The aims of COPD management Reduce symptoms: Relieve

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 guidelines www.goldcopd.org

Improving the Differential Diagnosis of Chronic Obstructive Pulmonary Disease in Primary Care www.goo.gl/ZraLr

American Lung Association www.lung.org/lung-disease/copd/

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50 January 2013 Calendar

January 2013

Calendar

January

16th Bangkok International Symposium on HIV Medicine

16/1/2013 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: jeerakan.j@hivnat.org Website: www.hivnat.org/bangkoksymposium

28th Congress of the Asia-Pacific Academy of Ophthalmology

17/1/2013 to 20/1/2013 Location: Hyderabad, India Info: APAO Secretariat Tel: (852) 3943 5827 Fax: (852) 2715 9490 Email: secretariat@apaophth.org Website: www.apaoindia2013.org

Emergency Medicine 2013

23/1/2013 to 24/1/2013 Location: London, UK Info: MA Healthcare Conferences (London) Tel: (44) 20 7501 6762 Fax: (44) 20 7978 8319 Email: conferences@markallengroup.com Website: www.mahealthcareevents.co.uk/

4th International Conference on Legal Medicine, Medical Negligence and Litigation in Medical Practice (IAMLE-2013)

25/1/2013 to 27/1/2013 Location: Thiruvananthapuram, Kerala, India Info: Prof. R.K.Sharma, Chairman - IAMLE 2013 Tel: (91)11 4158 6401/402 Email: rksharma1@gmail.com, info@dreamztravel.net Website: www.iamleconf.in

February

Food Allergy and Anaphylaxis Meeting (FAAM)

2013

7/2/2013 to 9/2/2013 Location: Nice, France Info: EAACI FAAM 2013 Secretariat Tel: (33) 1 7039 3554 Fax: (33) 1 5385 8283 Email: infoFAAM2013@mci-group.com Website: www.eaaci-faam.org/

International Meeting on Emerging Diseases and Surveillance (IMED 2013)

15/2/2013 to 18/2/2013 Location: Vienna, Austria Info: International Society for Infectious Diseases Tel: (617) 277 0551 Fax: (617) 278 9113 Email: info@isid.org Website: www.isid.org/imed/Index.shtml

Asian Pacific Society of Cardiology 2013 Congress

21/2/2013 to 24/2/2013 Location: Pattaya, Thailand Info: Kenes Asia (Thailand Office) Tel: (66) 2 748-7881 Fax: (66) 2 748-7880 Email: apscoffice2013@apsc2013.org Website: www2.kenes.com/apsc2013/pages/home.aspx

March

23rd Conference of the Asia Pacific Association for the Study of the Liver

7/3/2013 to 10/3/2013 Location: Singapore Info: Gastroenterological Society of Singapore, The Asian Pacific Association for the Study of the Liver Tel: (65) 6292 4710 Fax: (65) 6292 4721 Email: apaslconference@kenes.com Website: www.apaslconference.org

62nd American College of Cardiology (ACC) Annual Scientific Session

9/3/2013 to 11/3/2013 Location: San Francisco, California, US Info: American College of Cardiology Foundation Tel: (415) 800 699 5113 Email: accregistration@jspargo.com Website: www.accscientificsession.org/Pages/home.aspx

28th Annual European Association of Urology Congress

15/3/2013 to 19/3/2013 Location: Milan, Italy Info: European Association of Urology Tel: (39) 2 4342 6275 Fax: (39) 2 4801 0270 Email: info@eaumilan2013.org Website: www.eaumilan2013.org

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51 January 2013 Calendar

January 2013

Calendar

4th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association

27/3/2013 to 30/3/2013 Location: Shanghai, China Info: Asian Pacific Hepato-Pancreato-Biliary Association Tel: (86) 21 350 30066 Fax: (86) 21 655 62400 Email: secretariat@aphpba2013shanghai.org Website: www.aphpba2013shanghai.org

April

European Congress on Osteoporosis and Osteoarthritis

17/4/2013 to 20/4/2013 Location: Rome, Italy Info: International Osteoporosis Foundation Tel: (32) 4 254 1225 Email: info@iofbonehealth.org Website: www.ecceo13-iof.org

48th European Association for the Study of the Liver

24/4/2013 to 28/4/2013 Location: Amsterdam, Netherlands Info: European Association for the Study of the Liver Tel: (31) 20 549 1212 Fax: (31) 20 646 4469 Email: devi.sonida-mey@easloffice.eu Website: www.easl.eu/_the-International-liver-congress/ general-information

5th Association of Southeast Asian Pain Societies Conference

28/4/2013 to 5/5/2013 Location: Singapore Info: Pain Association of Singapore Tel: (65) 6292 4710 Fax: (65) 6292 4721 Email: aseaps2013@kenes.com Website: www.aseaps2013.org Tel: (86) 21 350 30066 Fax: (86) 21 655 62400 Email: secretariat@aphpba2013shanghai.org Website: www.aphpba2013shanghai.org

(86) 21 350 30066 Fax: (86) 21 655 62400 Email: secretariat@aphpba2013shanghai.org Website: www.aphpba2013shanghai.org
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52 After Hours January 2013

After Hours

January 2013

52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
Radha Chitale
Radha Chitale
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na
52 After Hours January 2013 Radha Chitale T he kitchens at Mount Elizabeth Nove - na

T he kitchens at Mount Elizabeth Nove-

na Hospital fire up at 5 each morning.

Chefs at seven different stations begin

at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus
at 5 each morning. Chefs at seven different stations begin chopping vegetables, cooking rice, reviewing menus

chopping vegetables, cooking rice, reviewing menus and making preparations for break- fast. Executive Chef Alan Sim stops by each section every day to check a recipe or tweak a garnish. Each meal is calibrated to precise amounts of calories, fats, vitamins and miner- als and carefully vetted by dieticians. With such a clinical approach, it is no won- der that “hospital food” is not usually asso- ciated with gastronomic heights; more along the lines of bland, wilting fare, to be endured like another hospital procedure. But if patients don’t eat – because they have no appetite, because they don’t like the food being served – they are missing the nutrition that is a critical part of care and recovery. Pa- tients who eat the least tend to have the worst clinical outcomes and are at increased risk of malnutrition. [Nutr Clin Pract 2012;27:274-80] Behind the scenes of many of Singapore’s hospitals, teams of chefs, nutritionists and di-

hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that
hospitals, teams of chefs, nutritionists and di - eticians work to put together healthy menus that

eticians work to put together healthy menus

and di - eticians work to put together healthy menus that don’t compromise on flavor. “We
and di - eticians work to put together healthy menus that don’t compromise on flavor. “We
and di - eticians work to put together healthy menus that don’t compromise on flavor. “We

that don’t compromise on flavor. “We need to provide food that will change

on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
on flavor. “We need to provide food that will change Alan Sim William Tay SERVE UP
Alan Sim William Tay
Alan Sim
William Tay

SERVE UP HEALTHY GOURMET ON A TRAY

Alan Sim William Tay SERVE UP HEALTHY GOURMET ON A TRAY the entire perception of hospital
the entire perception of hospital food,” Sim said. Know thy dish Sim’s background is largely
the entire perception of hospital food,” Sim
said.
Know thy dish
Sim’s background is largely in hotel kitch-
ens, like many chefs who have found their way
to the health care industry. They are no strang-
ers to producing meals on a large scale. A large
public hospital like Singapore General Hospi-
tal (SGH) serves about 4,000 meals per day.
But cooking within rigid nutritional guide-
lines can pose a challenge for chefs used to
prioritizing flavor.
To help kitchen staff understand how to
put together a balanced meal, hospital dieti-
cians brief them on nutrition, dietary guide-
lines, therapeutic diets for diabetic or cancer
patients, for example, and how to use substi-
tute ingredients based on patient needs.
For normal meals, hospitals follow the di-
etary guidelines recommended by the Minis-
try of Health. However, a diabetic patient will
need meals that contain less sugar and more
vegetables. A hypertensive patient will need
meals low in salt. Meals may also need to be
altered for vegetarian or Halal requirements.
“I have to be precise. I need to know what
makes it into the ingredients and composition
of a dish and also the nutrients that go into
that,” said Ms. Poh Leng, one of the dieticians
53
53
53 After Hours January 2013

After Hours

January 2013

who worked with Sim to develop the menu at Mount Elizabeth No- vena. “That way,
who worked with Sim to develop the menu at Mount Elizabeth No-