Robotic navigation set to guide arrhythmia treatment in SE Asia

Medical Tribune October 2009 P4
David Brill

Cardiac arrhythmia patients can be treated faster, more safely and with less radiation exposure, following the unveiling of a cutting-edge robotic system at the National Heart Centre Singapore (NHCS).

The technology allows electrophysiological catheter ablation to be done by remote control, using magnets to guide the catheter to its target with dexterity that cannot be achieved by hand.

Cardiologists direct proceedings from a computer workstation – sparing them from neck and back pain that can result from manual ablation procedures, which last up to 6 hours. Procedural time is expected to drop to 2-3 hours with the magnetic navigation system.

Twelve patients have already been treated with the system, which is the first of its kind in Southeast Asia.

“The robotic magnetic navigation system can allow us to safely map the heart to 1 to 2 mm accuracy and precision without the use of fluoroscopy,” said Dr. Teo Wee Siong, director of electrophysiology and pacing and senior consultant cardiologist at NHCS.

“This precision cannot be achieved by conventional ablation with our hands manually, no matter how skilled we are. This will definitely improve patient outcome and safety, especially in complex arrhythmia cases such as atrial fibrillation and ventricular tachycardia,” he said.

The procedure eliminates physician radiation exposure and lowers patient exposure by 40 percent compared with conventional ablation. The new catheters are also softer and more flexible than manually operated versions, thereby reducing the risk of damaging the heart walls from 2-3 percent to less than 1 percent.

The feasibility of magnetic navigation systems for catheter ablation was first demonstrated 7 years ago in dogs and pigs. [Circulation 2002;106:2980] The intervening years have seen the technology evolve and progress to human usage, with centers in the US, Italy and Germany among the first to report their results. Some procedural times were initially longer than conventional ablation, but have shortened with growing experience.

Most recently, the Texas Cardiac Arrhythmia Institute, US, reported success in 164 of 193 robotic catheter ablations (85 percent), compared to 159 of 197 manual ablations (81 percent). Mean exposure to fluoroscopy was slightly increased for the first 50 procedures performed with the robotic system (61.8 minutes versus 58.4 minutes for conventional ablation), but dropped to 44.5 minutes over subsequent procedures. [J Cardiovasc Electrophysiol 2009 Jul 28; Epub ahead of print]

NHCS sees around 300 patients each year requiring catheter ablation and an implantable cardioverter-defibrillator. It estimates that around 60 percent of cases could be treated with the new magnetic navigation system.

Singapore center set to tackle childhood cancer in Asia

Medical Tribune April 2009 SFIV

David Brill

A new Singapore center could help raise childhood cancer survival rates across Asia, thanks to a recent $24 million funding boost.

The money will expand treatment facilities and strengthen research at the Viva-University Children’s Cancer Centre, which has already treated some 40 overseas children and begun training visiting specialists.

Around four out of five children with leukemia are cured in Singapore but in nearby countries this figure can be as low as one in 20.

“There is an urgent need for us to respond to the cries of children with cancer in Singapore and the whole region,” said Mrs. Jennifer Yeo, director and secretary of Singapore-based Viva Foundation for Children with Cancer.

“We are confident that with the support of all our donors, volunteers and strategic partners we can save many young lives,” she said.

The center, known as VUC3, has been operational for a year but was officially opened last month. Two specialists from the Philippines have already trained there, and one each from Myanmar and Brunei are currently in training.

The new funding comprises a $12 million gift from the Goh Foundation – a nonprofit private group – matched like-for-like by the Singapore government.

Four main research programs will be established, comprising bone marrow transplantation, childhood leukemia, bone cancer and ‘after completion of therapy,’ which focuses on the long-term impact of cancer treatment. This research will have a strong translational clinical focus with a view to raising cure rates, lowering treatment costs and minimizing side effects, said Associate Professor Allen Yeoh, medical director of VUC3.

“This will provide us with a quantum leap in the care of childhood cancer in Singapore, and help ensure that no child dies in the dawn of life. In the current severe recessionary climate, we are truly grateful to the Goh Foundation for their generosity,” said Yeoh, also a consultant at the University Children’s Medical Institute, National University Hospital, which houses VUC3.

Pediatric cancer survival is “dismal” in low-income countries, according to a study published last year. Five-year survival in the Philippines was estimated at 10 percent and in Vietnam just 5 percent. [Lancet Oncol 2008 Aug;9:721-9]

Between 120 and 140 new pediatric cancer cases are diagnosed in Singapore each year – some 40 percent of which are leukemia. Around 40 local children have been treated at VUC3 so far.

The center has already installed five new bone marrow transplant rooms and raised the number of inpatient beds from 12 to 17. The funding has also helped establish the Viva-Goh Foundation Professorship in Pediatric Oncology.

VUC3, built at a cost of $5 million from the Singapore Tote Board and Viva Foundation, is working closely with the St. Jude Children’s Research Hospital in Memphis, US – one of the world’s leading childhood cancer centers.

Action needed on S. aureus in developing SE Asian countries

Medical Tribune March 2009 P12

David Brill

The burden of Staphylococcus aureus in low-income south and east Asian countries is poorly understood and could pose a threat to the health of both developed and developing countries, an international team of researchers has warned.

The lack of data on drug resistance rates in particular could exacerbate the problem if a strategic research program is not defined, the group wrote in a recent review in The Lancet Infectious Diseases. [2009 Feb;9(2):130-135]

The regional prevalence of methicillin-resistant S. aureus (MRSA), for example, remains largely unknown, although surveillance data from India and China suggest that the strain represents a substantial and rising proportion of the overall S. aureus burden. This knowledge gap could be contributing to the lack of recognition given to the problem by healthcare workers and the public, the study authors say.

The unregulated sale of cheap, substandard over-the-counter antibiotics could also be fuelling the emergence of MRSA in these countries, they add.

Mortality data on S. aureus in developing Asian countries are also scarce, but one study from a Thai hospital found that the death rate from bacteremia could be as high as 48 percent. [Lancet Infect Dis 2006 Feb;6(2):70-1] A comparable study in the US reported a mortality of just 22 percent. [Arch Intern Med 2003 Sep 22;163(17):2066-72]

Children seem particularly vulnerable to S. aureus in low-income countries in south and east Asia, unlike in high-income countries where the incidence of the bug appears largely to increase with age. The same study from Thailand found that S. aureus infections were most common in neonates, who made up 25 percent of all cases, while another study from Laos demonstrated that S. aureus was the number one cause of bacteremia in children aged under 1 year. [Am J Trop Med Hyg 2006 Nov;75(5):978-85]

“The burden of S. aureus disease in developing regions is inadequately appreciated or understood. An initiative is needed to raise the profile of S. aureus disease in developing countries, and to fund studies to better define the healthcare challenges and potential practical solutions relating to this important global pathogen,” wrote the authors, who hail from the Mahidol University in Bangkok, Thailand, the University of Oxford, UK, and the University of Washington in Seattle, US.

A total of 96 papers were included in the literature review – comprising published data from 20 low-income or lower-middle income countries including Indonesia, the Philippines, Vietnam and Cambodia.

Besides establishing the prevalence of MRSA, future research should also be directed at identifying risk factors for S. aureus and implementing cheap but effective mechanisms for infection control, the authors wrote.

Integrity and objectivity on trial: Rebuilding confidence

Medical Tribune March 2009 P16

The ongoing fallout from the withdrawal of rofecoxib in 2004 continues to expose the core values of the international research community to debate. In the second of a two part series, David Brill looks at the safeguards being put in place to prevent it from happening again, and finds out how Southeast Asia can play its part in helping to restore the damaged reputation of medical research.


When the integrity of medical science is threatened, “patients, clinicians and researchers are all at risk of harm, and public trust in research is jeopardized,” wrote the editors of the Journal of the American Medical Association in an editorial last year. “Ensuring, maintaining, and strengthening the integrity of medical science must be a priority for everyone,” they concluded. [JAMA 2008; 299(15):1833-1835]

The trigger for this call to action was the publication of two new papers shining yet more light into the uncomfortable darkness surrounding the withdrawal of rofecoxib. With every painful new insight revealed by the ongoing litigation process – these latest revelations alleged the ghostwriting of manuscripts and the questionable presentation of mortality data in key clinical trials – the restoration of this integrity seems an ever-more distant target. [JAMA 2008;299(15):1800-12; JAMA 2008;299(15):1813-7]

The task is one that faces the entire medical profession, but for Professor Jeffrey Drazen, editor-in-chief of the New England Journal of Medicine (NEJM), it has taken on a particularly personal significance. The journal became an unwitting accomplice in the rofecoxib affair when it published the Vioxx Gastrointestinal Outcomes Research (VIGOR) study – later to be tainted for its omission of three late-breaking myocardial infarctions. [N Engl J Med 2000;343:1520-8; N Engl J Med;2005 353:2813-4] The saga, he says, has “changed the rules” for medical journal editors.

The NEJM, for its part, is fighting on several fronts to ensure the objectivity of the research contained within its pages. Along with other major medical publications, the journal now stipulates that clinical trials be registered in an international database – a requirement which prevents the changing of protocols mid-trial and creates an internationally-harmonized norm, Drazen says. The editors have also learned to demand personal accountability for the data, request longer adverse event reporting, and be more aggressive about querying authors when they feel that there are discrepancies, he adds.

Drazen believes, however, that the long-term solution to the rebuilding process lies out of the hands of the journals and at the very heart of medical research training. “People need to understand that you’re not here to make the boss happy – you want to report the truth,” he says. “In all research we need to teach this culture that [focuses on] getting it right, not just getting it published. Publishing papers is a way to gain fame and reputation, but if you publish a lot of papers that are wrong you’ll start off on a high but you’ll crash.”

The damage to the reputation of medical research has perhaps been most keenly felt in the US, but for Southeast Asia the stakes are equally high. As the region continues to promote itself as a biomedical research hub, financial and commercial interests in its countries grow, and the potential for disaster increases. And with the shadow of Dr. Hwang Woo Suk, the discredited South Korean stem cell scientist, still looming large, the need for adequate ethical safeguards in the region is beyond question.

Singapore, for one, appears already to be taking action to ensure the future integrity of its research. Ethics feature prominently in the nation’s Good Clinical Practice (GCP) Guidelines, a cornerstone of all research conducted in the country, and are also moving up the agenda at the Yong Loo Lin School of Medicine, which in September 2006 became the first medical school in Southeast Asia to open a dedicated academic center for biomedical ethics. At the national level, approval for clinical trials must be gained from the Health Sciences Authority, which scrutinizes all proposals before granting the required certificate.

Much of the responsibility for protecting the integrity of research, however, still lies at the doorsteps of the individual centers and their institutional review boards. Professor Fong Kok Yong’s role, as chairman of division research, is to promote and encourage research at Singapore General Hospital (SGH) – just one of several research centers in the country which prides itself on its publication output. He says that he is happy with the ethical safeguards that are presently in place, but stresses that it is an ongoing, “lifelong” process to instill the appropriate values in SGH’s researchers.

“Medical school is a good start but lectures are just laying some of the foundations,” he says, noting that researchers continue to learn from their peers through an informal mentorship network. The hospital has also been strengthening its educational agenda – offering additional courses and seminars which, Fong says, have been received with enthusiasm by researchers. A recently launched 2-day workshop, focusing on the ethics of GCP and involving speakers from both academia and industry, was heavily oversubscribed, he notes. SGH also implemented a “whistleblower” policy in 2007 to help protect the integrity of its research – allowing researchers to report fraudulent activities without fear of reprisals, and enabling an independent investigation to be undertaken.

Fong adds that it is important to maintain a balance where the frontiers of knowledge and technology can continue to be pushed but without sacrificing patient safety in the process. “As in all things in science, to compete is good, but we don’t want people to compete at all costs. At SGH I think there is a balance – we want to emphasize that it’s not so serious that if you don’t publish you will perish,” he says.

Although Southeast Asia has so far been spared the type of incident where patients are put at risk, the research community here must continue to strengthen its defenses, according to Dr. Thiru Thirumoorthy, a former director of the Singapore Medical Association’s Centre for Medical Ethics and Professionalism. He believes that the rofecoxib story should serve as a wake-up call for the rest of the world, and draws attention to the wider ethical issues of conflicts of interest and the relationships between doctors and pharmaceutical companies.

“Of course the pharmaceutical industries are much bigger in the US so they have greater stakes, but this is by no means purely an American condition,” he says. “The lesson to learn is for us not to reach this point. We should have already put up our barriers much earlier.”

Thirumoorthy believes that in Singapore, in general, the relationships between academia and industry are relatively well moderated at present, but notes that in the absence of definitive evidence the community should remain on guard against complacency. “The first question we need to ask is do we have a problem and is it severe enough for us to do something more? At the moment there is no obvious evidence that it has reached a stage of an exploitative nature. There may be incidences that we do not know of but until such time we should continue to work on education and enforcing guidelines to improve the situation.”

Ultimately, however, only time will tell whether the global medical community is doing enough to protect itself, and whether the public’s faith in medical research can ever be fully restored. Despite the profession’s best attempts to tighten its defenses, it may simply be a matter of time until its values are once again left cruelly exposed.

“We’re doing our best to try to keep people honest but I’d be a fool to say that it won’t happen again,” concludes Drazen. We’re protecting against things that happened in the past but somebody will be creative and come up with something new and there’s nothing you can do about it. If someone wants to cheat badly enough, they’ll succeed.”

Professor Jeffrey Drazen was in Singapore as part of the National University Health System’s Distinguished Editors Series.

Southeast Asia aligns with JUPITER

Medical Tribune February 2009 P9
(Indonesia / Philippines edition only)
David Brill

Experts in Southeast Asia are responding with cautious optimism to the landmark JUPITER* study, which dominated headlines at the recent American Heart Association conference in the US.

While there are several important messages to draw from the study doctors should not rush to incorporate the findings into routine practice, specialists from the region told Medical Tribune.

Local guidelines are not anticipated to change in the immediate future, they said.

JUPITER – a randomized controlled trial of 17,802 participants – demonstrated that rosuvastatin, as compared to placebo, significantly reduced major cardiovascular event rates in overtly healthy people with normal LDL-cholesterol but elevated high-sensitivity C-reactive protein (hsCRP) levels. [N Engl J Med 2008 Nov 20;359(21):2195-207] The study has moved hsCRP into the limelight and prompted some international experts to call for the biomarker to take a more prominent role in cardiovascular risk stratification.

Professor Cheuk-Man Yu, head of the division of cardiology at the Chinese University of Hong Kong, said that the reduction of cardiovascular events in the study was “highly encouraging” for both physicians and patients but noted that more research is still needed into the pathophysiological mechanisms that underlie the effect.

“It will be difficult to generalize this into routine practice without further understanding the relationship between lipid lowering, reduction of vascular inflammation and reducing atherosclerosis,” he said.

“I don’t think we fully understand the hsCRP story. From this study it does seem to be a very important mediator for underlying vascular disease but we still haven’t got the definite answer as to whether it is a stand-alone risk factor or just a manifestation of the accumulated conventional risk factors.”

hsCRP levels can be altered by a number of factors and may not be solely a marker of inflammation in vascular plaques, said Yu, noting that bacterial and viral infections, rheumatoid arthritis, tuberculosis and lupus erythematosus can all increase levels of the biomarker. These potential explanations would all need to be ruled out, and all conventional risk factors worked upon, before considering intervention on the basis of an elevated hsCRP alone, he said.

Associate Professor Terrance Chua, chairman of the Singapore Heart Foundation, said that he expects hsCRP testing to “take on a bigger role” in risk assessment, in light of the data from JUPITER.

“It would be useful in a situation where a patient is at intermediate risk and one is trying to make a decision whether or not to initiate lipid-lowering therapy. hsCRP may help to further refine the risk and cast the deciding vote on whether or not to start treatment in these patients. We will have to wait and see how the guidelines committee absorbs this information,” he said.

Chua also noted that the JUPITER results are consistent with those of previous statin trials and provide further reassurance as to the benefits of cholesterol-lowering therapy. He added, however, that it is important not to lose sight of the importance of non-pharmaceutical interventions such as diet.

“The great challenge is really to try to change lifestyle,” he said. “It’s a bigger challenge than taking a tablet but if we want to have a truly cost-effective way of dealing with the growing problem then changing lifestyle would obviously be more effective.”

Dato’ Seri Dr. Robaayah Zambahari, senior consultant cardiologist at the National Heart Institute in Kuala Lumpur, Malaysia, said that she believes strongly in the benefits of statins for secondary prevention but that the risk-to-benefit ratio will need to be reviewed before adopting a primary prevention strategy.

She added that JUPITER did not address the long-term safety of rosuvastatin since the trial was stopped after just 1.9 years.

-------------------------------------------------
*Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

Experts fear rise of drug-resistant superbug

Medical Tribune January 2009 P1&6
David Brill

Rising levels of drug resistance among Acinetobacter Baumannii are causing serious concern among infectious disease experts, who are calling for urgent international attention to the issue.

The bug is particularly prevalent in hospitals in Southeast Asia, with Taiwan and Korea seemingly the worst affected.

The rapidly dwindling number of treatment options could soon herald the dawn of the “post-antibiotic era,” according to a specialist from Singapore, where extensively drug-resistant strains have already been reported.

A. Baumannii resistance rates are increasing globally, with around half of strains presently thought to be resistant to at least one antibiotic. Nearly 20 percent of strains are resistant to all but one or two agents.

Reports have already emerged of pandrug resistant strains, which – although rare at present – will beome increasingly common if the problem is not addressed, said Professor Matthew Falagas, an international expert who published a recent high-profile review calling for more research into treatment options. [Lancet Infect Dis 2008 Dec;8(12):751-62]

“We should be worried because we have never heard before of bugs which affect humans where we do not have an antibiotic to provide,” he told Medical Tribune.

“The issue of pan-drug resistance needs international attention. Public health organizations and local infection controls at the country level should disseminate guidelines on this issue,” he said, adding that in some hospitals the significance of the bug is already on a par with methicillin-resistant S. Aureus (MRSA).

A. Baumannii mainly affects seriously ill patients in intensive care units and burn wards. Although less common than other hospital-based infections, the bug can cause significant morbidity and mortality, placing a heavy drain upon hospital resources through repeated hospitalizations and increased lengths of stay.

A Singapore study found that 69 percent of A. Baumannii strains in one intensive care unit were resistant to carbapenem. Nearly 20 percent of isolates from all the nation’s hospitals were resistant to everything except the polymixins, which can cause significant toxicity to the brain and kidneys. [Emerg Infect Dis 2007 Dec;13(12):1944-7]

“Its ability to acquire resistance is a big concern because there aren’t going to be many treatment options available,” said Dr. Tan Thuan Tong, an infectious diseases consultant at Singapore General Hospital.

“We foresee a time when you get strains that are not treatable and you just try your luck with various combinations that might act in a synergistic manner,” he said, adding that such a scenario could arise in Singapore within the next 5 years.

Around 30 to 40 percent of patients who get a multidrug-resistant A. Baumannii bloodstream infection may die, according to Tan, but he added that the directly attributable mortality is not clear-cut since patients are often critically ill for other reasons.

Falagas, meanwhile, called on hospitals worldwide to decrease the usage of antibiotics and promote stricter infection prevention and control measures, particularly with regard to hand hygiene. He added that research is now ongoing to find new antibiotics for Gram-negative bacteria, but said that the process has been too slow getting started.

“The scientific community and the pharmaceutical companies have focused attention on Gram-positives without understanding the significance of Gram-negatives as healthcare-associated infections, and especially A. Baumannii,” said Falagas, who is director of the Alfa Institute of Biomedical Sciences in Athens, Greece, and an adjunct associate professor at Tufts University
School of Medicine, Boston, US.

Singapore has already begun to acknowledge the growing problem of antimicrobial resistance, with a group of experts publishing a recent position paper advocating stricter controls on the use of antibiotics. [Singapore Med J 2008 Oct;49(10):749-55]

“In the 18th and 19th century, there were no antibiotics and treatment was with drainage of pus, amputation and other surgical approaches. If you have infections with these untreatable bugs, then you are back to the days when you can’t do anything,” added Tan.

Asia takes action on drug-resistant tuberculosis

David Brill
The Lancet Infectious Diseases October 2008
Article link

This article also appeared on the Stop TB homepage of the WHO's Western Pacific Region Office.

Africa and eastern Europe have largely dominated recent attention around strengthening tuberculosis control, but Asia could yet prove the decisive battleground in the international war on the disease. At a gathering of countries from WHO's Western Pacific Region (WPR) in Tokyo (July 22—24) Pieter van Maaren, regional advisor for tuberculosis (WHO, Manila, Philippines), accused Asian nations of complacency, saying: “if we are going to avoid a public-health disaster, we have to accelerate action”. Representatives from all eight of the countries that attended—representing around 95% of the region's multidrug-resistant (MDR) tuberculosis burden—acknowledged the issue and agreed to raise their commitment to it.

The WPR alone makes up a quarter of the world's tuberculosis cases—a similar proportion to Africa. Together with the South-East Asia Region (SEAR), more than 300 000 cases are estimated to be MDR, with only 1% of patients accessing appropriate treatment. The prevalence of MDR tuberculosis is highest in China (one in every ten new tuberculosis cases), which remains second only to the former Soviet Union in terms of prevalence.

Strengthening diagnostic laboratory facilities is a major component of WHO's strategy for the control of MDR tuberculosis in the region. Senior laboratory managers from the WPR will be attending a workshop in Hong Kong in October to discuss how to implement the latest technologies, including molecular line probe assays that can give a diagnosis of MDR tuberculosis in 2 days. These tests are being introduced through a UNITAID-funded project, announced in June. Laboratory capacity is a serious concern in the SEAR, which is home to only two of the 26 centres in WHO's global Supranational Laboratory Network, a network that provides assistance with MDR-tuberculosis testing to national facilities.

“For us in this region the emphasis is on using this window of opportunity to put in cost-effective interventions to prevent MDR tuberculosis. It's less about trying to catch people once they've developed MDR disease, which is what we are seeing in eastern Europe and in Africa, but rather building that barrier to stop people developing MDR tuberculosis in the first place”, said Nani Nair, SEAR's regional tuberculosis advisor (WHO, New Delhi, India).

In Tokyo, delegates also promised to commit to providing better access to treatment, with countries being encouraged to submit proposals to the Global Fund to finance the purchasing of drugs for MDR tuberculosis. Management programmes supported by the Green Light Committee are currently operating in six SEAR countries, while UNITAID funding is available for drug procurement in three.

Nair told TLID: “…if all current plans can be implemented successfully then the long-term outlook for control of MDR in the SEAR is very good”. At present, however, she estimates that only half the required budget has been raised. The region does not contain any major international donors, and to make up this shortfall countries must rely on funding from their own governments, donors from other regions, and international initiatives such as the Global Fund and UNITAID.

China meanwhile is looking into health-care reforms and how they can be integrated into scalable new programmes for MDR-tuberculosis treatment and control. In the wake of the severe acute respiratory syndrome epidemic in 2003 it became a legal requirement for health-care systems to report all new tuberculosis cases within 24 h. Individual patients from across the country are now entered into an online database and can be tracked centrally to ensure that they receive appropriate treatment.

The project has caught the attention of the Bill & Melinda Gates Foundation, who have pledged to spend some US$900 million on tuberculosis worldwide by 2015. Representatives from the Foundation have been in discussions with the Chinese government about how new diagnostic technologies can be integrated into this system to detect multidrug resistance at the first point of contact. “Their surveillance system is phenomenal, and they've scaled it up so that 90% of their referral hospitals are using it. Having these online mechanisms for tracking tuberculosis cases and ensuring that those patients get optimal therapy lays the foundation for a truly innovative programme for controlling MDR tuberculosis that goes beyond the standard interventions”, said Senior Program Officer for Tuberculosis Peter Small (Bill & Melinda Gates Foundation, Seattle, WA, USA), who recently returned from a fact-finding trip to the country. He added that he was “very impressed by the government's commitment” to tackling MDR tuberculosis.

How current efforts to control MDR tuberculosis in Asia will affect the longer-term global spread of the disease remains to be seen. Small is in no doubt, however, as to the importance of the task. “What the world is doing with MDR tuberculosis right now, through inaction, is committing ourselves to a future epidemic of much more complicated tuberculosis. I suspect that future generations will judge us harshly if we fail to intervene”, he said.

Images courtesy of WHO/P Virot.

Asia-Pacific researchers launch trial for combined liver cancer therapy

Medical Tribune August 2008 SFIX
David Brill

An international team of researchers has begun a study into a combination therapy that could prolong the lives of patients with inoperable hepatocellular carcinoma (HCC) – a cancer that is particularly common in Asia.

Thirty one patients will participate in the 2-year phase I/II trial, which aims to combine the oral chemotherapy drug sorafenib (400mg twice daily) with radiation therapy delivered by Selective Internal Radiation (SIR)-Spheres®.

The primary objectives are to assess the tumor response rate and the safety and toxicity of the therapy. Survival, recurrence rates and quality of life are among the secondary outcomes to be investigated.

The study is being carried out by The Asia-Pacific Hepatocellular Carcinoma Trials Group, which is based at the National Cancer Centre Singapore (NCCS). Centers in 12 different countries, including Malaysia, Indonesia and Philippines, have so far been invited to participate.

Professor Soo Khee Chee, director of the NCCS, said that the team was “especially pleased” to announce the trial, adding that he was confident it would produce very strong data.

“This trial is an important milestone for all our researchers and clinician investigators because we will be taking a step forward in our efforts to help our patients combat liver cancer,” said Soo.

The chair of the trial, Associate Professor Pierce Chow, said that HCC is particularly prevalent in Asia owing to high rates of hepatitis B, which is the major cause of the cancer. He said that there was anecdotal evidence to suggest that the combination therapy was promising for HCC patients, but added that it is imperative that scientific data be gathered appropriately from clinical trials.

The high cost of the two treatments is also an important consideration according to Chow, who is a senior consultant surgeon at Singapore General Hospital. Sorafenib costs a patient around S$9,000 per month at NCCS, whereas SIR-Sphere therapy could cost up to S$20,000, he said.

Funding for the trial comes in the form of a S$468,200 grant from Singapore’s National Medical Research Council. Bayer Schering Pharma Singapore, who produce sorafenib, and Sirtex Medical Ltd, who manufacture the SIR-Spheres®, are each providing around S$1.5 million worth of therapeutics.

Sorafenib targets the proliferation of tumor cells and angiogenesis. Data from a Phase III trial, presented in 2007 at the annual meeting of the American Society of Clinical Oncology, showed that the drug extended overall survival in inoperable HCC patients by a median of 3 months but did not induce tumor regression.

SIR-Spheres®, conversely, induce a significant tumor response but trial data have yet to demonstrate an improvement in survival rates Chow said. The therapy involves delivering very high dose radiation directly to the tumor via a catheter, thereby sparing the healthy surrounding tissues.

Singaporean medical team reports back from Burma

BMJ 21 June 2008
Link
David Brill

Although some humanitarian organisations are still encountering obstacles in providing aid to the survivors of the cyclone that hit Burma in May, a team of doctors and nurses from Singapore has been able to treat some 5000 patients.

The team of 23, now back home, was based for two weeks at a hospital in the township of Twan Te, roughly an hour’s drive south west of Rangoon. Dispatched under three separate banners—the Ministry of Health, the Singapore Red Cross, and a non-governmental humanitarian charity called Mercy Relief—they united on arrival to share expertise and resources.

Some international aid had reached the people of Twan Te, many of whom are living in tented refugee camps with access to water filtration systems donated from overseas. Other residents had taken shelter in the town’s monasteries.

Rebuilding of damaged houses has already begun, the Singaporean team says. Many homes had lost their roofs and provided no shelter.

The team was restricted to the local province, which has a population of around 250 000, but were free to roam within it. They later set up mobile clinics and travelled by boat to some of the region’s more remote villages.

"These areas had no medical facilities, no doctors, and no nurses," said Arif Tyebally, leader of the health ministry’s team. "Some of them had health centres, but they were badly damaged by the cyclone, and there had been no medical help since then."

Access to clean water was also limited in the more isolated areas, and many villagers were drinking from contaminated wells.

At the peak of their operations the Singaporeans treated up to 600 patients each day. Gastroenteritis, chest infections, and skin infections were the most common ailments—typically resulting from the contaminated water in the villages or the poor sanitation and crowded living conditions in the township’s refugee camps.

The team also encountered mosquito-borne diseases such as malaria as well as fractures, burns, and abrasions that had remained untreated since Cyclone Nargis struck on 3 May.

Fatimah Lateef, a senior consultant from Singapore General Hospital who was working with Mercy Relief, reported that signs of post-traumatic stress disorder were common and were evident in children as young as 3 years old.

Even people who were not victims of the cyclone sought attention from the team, and patients with untreated chronic diseases such as diabetes and hypertension were often found in the queue at the clinics.

As they were limited to Twan Te province, the members of the Singapore team were unable to reach the worst affected areas in the Irrawaddy delta, where eyewitness reports have emerged of bodies trapped in trees. Closer to Rangoon the dead had been removed before the team from Singapore arrived.

"It probably was a problem closer into the delta, but we were not there, so I can’t speak at first hand. But from what we’ve heard some may have been left to decompose, and some may have been cleared," said Dr Tyebally, who previously took part in relief missions to Aceh in Indonesia after the tsunami in 2004 and Muzzaffarabad, Pakistan, after the earthquake in 2005.

Dr Lateef, also a veteran of relief missions in Asia, denied that the lack of access to the delta region was a source of frustration to the team. Preferring to focus on the coverage they provided in their allotted area, she said, "When we mount a humanitarian mission we have to respect the sovereignty and the rights of the country."

She reported that the Burmese officials were cooperative, particularly in providing translators and assisting the team in their travel around the region.

The Singapore team arrived in Burma on 22 May, three days after an agreement was reached at a meeting of the Association of Southeast Asian Nations to allow aid in from neighbouring countries.

The Red Cross team brought more than $S20 000 (£7400; 9400; $14 600) worth of medical supplies on their relief mission, including drugs, surgical equipment, intravenous infusion sets, syringes, thermometers, and bandages. The delegation from the health ministry flew out with 250 kg of supplies and was reinforced with a further 730 kg three days later.

As supplies ran low the team began to seek out further stocks in Rangoon, where much of the aid from other countries has ended up, and typically received a new delivery every two or three days.