New HIV strain came from gorillas

Medical Tribune September 2009 P3

French scientists have identified a new strain of HIV, which appears to have evolved in gorillas before crossing the species divide.

The virus has a distinct lineage from other HIV strains – notably the one chiefly responsible for the current AIDS pandemic, which is thought to have reached humans from chimpanzees. The researchers, who found the virus in a 62-year-old Cameroonian woman living in Paris, propose calling the new strain HIV-1 group P.

“The discovery of this novel HIV-1 lineage highlights the continuing need to watch closely for the emergence of new HIV variants, particularly in western central Africa, the origin of all existing HIV-1 groups,” they wrote.

[Nat Med 2009 Aug;15(8):871-2]

New fears raised over hormone therapy cancer risk

Medical Tribune September 2009 P3

A new study of almost a million people has strengthened the link between postmenopausal hormone therapy and the risk of developing ovarian cancer.

Danish researchers reviewed registry data from 909,946 women aged 50 to 79, over an average of 8 years of follow up. They found that hormone therapy users had an incidence rate ratio of 1.38 (95 percent CI 1.26 – 1.51) for all ovarian cancers, compared to women who had never used therapy. Cancer risk was increased “regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type and route of administration,” the authors wrote.

“Thus the risk of ovarian cancer is one of several factors to take into account when assessing the risks and benefits of hormone use,” they concluded.

[JAMA 2009 Jul 15;302(3):298-305]

Study flaws hinder review of TCM for stroke

Medical Tribune September 2009 P3

The poor quality of published data prevents a proper assessment of the efficacy of traditional Chinese medicine (TCM) remedies for stroke, a study suggests.

Despite finding 11,234 journal articles on TCM post-stroke therapies, the researchers from Italy and China were unable to conduct a meta-analysis as intended. Thirty four randomized controlled trials (RCTs) were found, but wide variation in the studies prevented them from being pooled. Moreover, all but one RCT reported results in favor of TCM, prompting the authors to suggest a “strong publication bias.”

“The key to lead to evidence-based practices is establishing a consensus on standardized relevant outcome measures and then designing and conducting appropriate RCTs that adopt those standards,” they wrote.

[Stroke 2009 Aug;40(8):2797-804]

Famotidine protects against aspirin GI damage

Medical Tribune September 2009 P6
David Brill

Histamine H2-receptor antagonists can limit the gastrointestinal side effects of low-dose aspirin and could offer a viable alternative to proton-pump inhibitors (PPIs), a recent study suggests.

The randomized, phase III FAMOUS* trial found that 12 weeks of treatment with famotidine significantly reduced the incidence of gastric ulcers, duodenal ulcers and erosive esophagitis compared to placebo.

The study, published in The Lancet, included 404 adults who were taking low-dose aspirin and had no ulcers or esophagitis at baseline. [2009;374:119-25]

Aspirin use continues to soar worldwide, yet there are few options for prevention of associated gastrointestinal complications. PPIs are known to be effective but have faced safety concerns – particularly over the risk of adverse interactions with clopidogrel.

“There is little doubt that aspirin and other anti-clotting drugs are very useful in the prevention of heart, brain, and other vascular diseases, hence their increasing use worldwide. Patients on such drugs should continue using them as advised by their family doctors or hospital specialists,” said the study’s lead author Dr. Ali Taha, of the University of Glasgow, UK.

“However, everybody should be aware that aspirin use can also be associated with a variety of gastrointestinal or digestive system problems, which sometimes can be serious. The results of this research widen the options for the prevention of such problems, particularly when more than one clotting drug is required,” he said.

Twelve weeks after randomization, 7 of 204 patients on famotidine had developed gastric ulcers, compared to 30 of 200 taking placebo (3.4 percent versus 15 percent; odds ratio 0.2; P=0.0002).

Just one patient developed a duodenal ulcer on famotidine, compared to 17 on placebo (0.5 percent versus 8.5 percent; OR 0.05; P=0.0045). Nine and 38 patients developed erosive esophagitis in the famotidine and placebo groups, respectively (4.4 percent versus 19 percent; OR 0.2; P<0.0001).>

Diabetic children often oblivious to hypoglycemia

Medical Tribune September 2009 P7

David Brill

Almost one in three children with type 1 diabetes cannot tell when their blood sugar dips low, and could face serious consequences from slipping into hypoglycemia, a study suggests.

A survey of 656 Australian children found that 29 percent had impaired awareness of hypoglycemia – a deficit in the adrenergic symptoms that ordinarily serve as a warning sign.

Children with impaired awareness were over twice as likely to have experienced a severe hypoglycemic episode in the previous year, involving loss of consciousness or seizure.

The effect was even more pronounced in the very young: children under 6 with impaired awareness were almost six times as likely to have had a serious episode.

Senior author Dr. Tim Jones said that hypoglycemia unawareness has traditionally been considered to be an adult problem, but urged physicians to step up screening among younger patients in light of the new findings.

“Ask the child: ‘do you get your usual symptoms? Do you still feel shaky when you go low? Or is the first thing you notice about being low that you find a low reading when you test yourself?’ It only takes a minute if you know what to ask,” he said.

Hypoglycemia unawareness appears to be caused by hypoglycemia itself, with repeated episodes successively dampening the adrenergic response, added Jones, head of the department of endocrinology and diabetes at Princess Margaret Hospital for Children, Perth, Australia.

The good news, however, is that the problem seems to some extent to be reversible, he said. Once impaired awareness is identified, the patient should meticulously ensure that they avoid hypoglycemia for around a month, and the warning symptoms may begin to return.

Further testing can also be carried out – particularly using continuous glucose monitoring systems to track a child’s blood sugar over time. This can help to identify and avoid episodes of hypoglycemia, regardless of whether the child is aware of it.

The study involved type 1 diabetic children aged from 6 months to 19 years. All were taking insulin – ranging from twice-daily injections to four times a day with insulin analogs and subcutaneous infusion therapy. [Diabetes Care 2009 Jul 8; Epub ahead of print]

A total of 161 hypoglycemic episodes had occurred in the year leading up to the study. The rate of episodes among children with impaired awareness was 37.1 episodes per 100 patient-years, compared to 19.3 per 100 patient-years in children with normal awareness.

Patients with impaired hypoglycemia awareness tended to be younger, had an earlier onset of diabetes, and had lower mean HbA1C levels since diabetes onset.

MIMS.com hailed for excellence in technology

Medical Tribune September 2009 P7
David Brill

Asia’s leading online drug database has been lauded for its innovative approach to digital technology at the recent Asian Multimedia Publishing Awards (AMPA).

MIMS.com – used by over 250,000 doctors and pharmacists in Asia – was named a runner-up in the ‘Use of Digital Technology’ category at the AMPA ceremony in Manila.

The award marks the 40th year of the directory, which is now used in 15 countries across the Asia-Pacific region and receives over 300,000 unique visitors each month. It was chosen out of 74 entries from 9 different countries.

Mr. Ben Yeo, Chief Executive Officer at CMPMedica Asia, publishers of MIMS and Medical Tribune, said: “This award commemorates the achievement that MIMS has attained in Asia at its 40th anniversary, further underscoring CMPMedica’s leading position in delivering drug information and scientific publishing in Asia. Our teams are keeping up their momentum in achieving the highest standards in the industry.”

The award makes CMPMedica the most highly decorated healthcare publisher at the Asian Publishing Convention, having previously picked up an award in 2007.

MIMS.com is used by doctors, pharmacists and healthcare professionals to access comprehensive drug information such as dosage, indications, safety and interactions. It is accessible online, and integrated within some hospital formularies.

Aspirin trial seeks to tackle colorectal cancer in Asia

Medical Tribune September 2009 P8
David Brill

A major new trial is set to launch in Asia to establish whether aspirin can prevent recurrence of colorectal cancer.

The ASCOLT study will involve over 2,000 patients from centers across Southeast Asia, China and India, and will be led jointly by the National Cancer Centre Singapore (NCCS) and the University of Oxford, UK.

Patients will be randomized to aspirin (200mg/day) or placebo for 3 years, following surgery and adjuvant chemotherapy for high-risk stage II and III colorectal cancer. The primary endpoint will be disease-free survival over 5 years of follow-up.

A growing body of evidence suggests that aspirin is effective for primary prevention of colorectal cancer, but ASCOLT is thought to be the first prospective clinical study to investigate the drug in the adjuvant setting after chemotherapy.

If positive, the results could have a huge impact on the treatment of colorectal cancer in Asia and worldwide, according to Dr. Toh Han Chong, head of the department of medical oncology at NCCS and one of the ASCOLT lead investigators.

“It’s incredible how many people you could save from relapse with the addition of aspirin if this study is positive. If you go to a village in India you can’t really give costly [monoclonal antibodies], so there is compelling power of social responsibility here,” he told Medical Tribune.

“We have undervalued the power of simple drugs. It’s time to redress the balance – change the paradigm and go cheap.”

Recruitment for ASCOLT is already underway, with centers confirmed in Singapore, Hong Kong, Jakarta and several cities in India.

More study centers are still needed in order to reach the target of 2,000 patients however said Toh, who extended the invite to all Asian delegates at the recent ‘Best of ASCO’ conference in Singapore.

“It’s a drug trial that cannot be done in the West. Many people over the age of 50 in the US are popping aspirin over the counter for heart conditions or stroke prevention,” he said. “Fewer people are on aspirin in Asia. That’s why it’s a perfect study to do here.”

Colorectal cancer is the second leading cause of cancer death in North America, Europe and Australasia according to a 2007 global report from the American Cancer Society. In Southeast Asia, it is the third biggest killer (behind liver and lung cancer) – responsible for 7.9 percent of cancer deaths.

In Singapore, colorectal cancer is the leading cancer among men and the second most common among women, data from the national cancer registry show.

A recent study found that regular use of aspirin after a diagnosis of colorectal cancer was associated with lower overall mortality (hazard ratio [HR] 0.79; 95% CI 0.53 – 0.95) and cancer-specific mortality (HR 0.71; 0.53 – 0.95), after a median of 11.8 years of follow-up. [JAMA 2009;302(6):649-58]

A 2007 paper, meanwhile, reported that taking 300 mg/day or more of aspirin for 5 years was effective for primary prevention of colorectal cancer, according to pooled data from two large randomized trials (HR 0.74; 95% CI 0.56 – 0.97; P=0.02). [Lancet 2007;369(9573):1603-13] Earlier trials have also shown that aspirin can prevent colorectal adenomas – the precursors to cancer – both in patients with, and without, a prior history of cancer. [N Engl J Med 2003;348(10):883-90; N Engl J Med 2003;348(10):891-9]

“Why should oncologists do an aspirin trial? Because the epidemiological data is strong, the data on polyp reduction is very convincing, the retrospective observational studies are very compelling and remarkable in terms of hazard ratios, and the data preclinically is scientifically robust,” added Toh.

ASCO award set to boost Asian cancer research

Medical Tribune September 2009 P8
David Brill

A Singapore oncologist has become the first Singaporean, and one of the first Asia-based recipients, to pick up a prestigious research award from the American Society of Clinical Oncology (ASCO).

Dr. Daniel Tan of the National Cancer Centre Singapore (NCCS) will receive a US$50,000 grant as part of the Young Investigator Award, bestowed by the ASCO cancer foundation.

The money will help fund his research on the molecular mechanisms of tyrosine kinase inhibitors (TKIs) in nasopharyngeal cancer. The work aims to understand why some patients respond better to targeted therapies than others – so as to improve patient selection and avoid unnecessary exposure to ineffective treatment and side effects.

“One of the challenges with any of these new-generation drugs is to find out how we can use them better – to get the right drug to the right patient. Understanding the reasons for response and resistance can also allow us to develop much more effective treatment strategies that hopefully translate to improved survival,” said Tan, who will work alongside his mentor Professor Teh Bin Tean, director of the NCCS-VARI laboratory – a joint project with the Michigan-based Van Andel Research Institute.

Tan’s ASCO proposal was borne out of clinical observations from a phase II trial of pazopanib, which saw a subset of nasopharyngeal cancer patients respond better to therapy than others. This trial is currently ongoing under principal investigator Dr. Darren Lim, a senior consultant at NCCS specializing in thoracic and head and neck cancers.

The goal now is to understand which proteins are targeted by the drug, and how this differs between patients and tumor types. Tan’s work will be done largely in a series of co-culture experiments and mouse xenograft models – allowing detailed analysis of how the drug affects each cellular compartment within a tumor.

Tan is also aiming to secure more local funding for his research, and hopes in the long term to help establish a comprehensive drug development program, which would also provide patients with access to novel therapeutic agents.

He added that he was pleased to receive the award, and is especially encouraged that the proposal was deemed to have sufficient scientific merit for further study.

“It is heartening to know that one’s ideas are being taken seriously by a highly regarded scientific body. Furthermore, the award is rarely given out to institutions outside of America, so it’s a nice endorsement of the research infrastructure at NCCS,” he said.

Cetuximab offers hope for Asian lung cancer patients

Medical Tribune September 2009 P8
David Brill

A novel lung cancer therapy could be of particular benefit to Asian patients, results of a recent trial suggest.

The international FLEX* study reported that adding the monoclonal antibody cetuximab to chemotherapy prolonged survival of advanced lung cancer patients from 10.1 months to 11.3 months.

Further analysis revealed, however, that Asians treated with the drug survived for a median of 19.5 months, whereas non-Asians survived only 9.6 months.

The randomized trial involved 1,125 patients – 121 of whom were from Asian centers (predominantly in Hong Kong, Taiwan, Singapore and South Korea). [Lancet 2009;373(9674):1525-31]

There are several possible explanations for the ethnic discrepancy but also questions that remain unanswered, according to Professor Kenneth O’Byrne, one of the FLEX investigators, who spoke to Medical Tribune during the recent ‘Best of ASCO’ conference in Singapore.

Asian lung cancer patients are more likely to be women, non-smokers and have adenocarcinomas than non-Asian patients – all groups which tend to survive longer, he said. Moreover, epidermal growth factor receptor (EGFR) mutations are more common among Asians – a characteristic which not only improves prognosis in itself, but also makes patients eligible for first-line EGFR tyrosine kinase inhibitors which can further improve outcomes.

“So there is a combination of reasons as to why but it’s not just that – there may be some intrinsic sensitivity to treatment here that’s not present in the West,” said O’Byrne, adding that further study is needed to better understand these biological similarities and differences.

Cetuximab is presently licensed for use only in colorectal and head and neck cancers. An application for lung cancer licensing was recently rejected by the European Medicines Agency (EMEA), but is currently under appeal from the manufacturer, Merck Serono.

The verdict has also come as a surprise to many experts in the field and will face “a strong challenge,” said O’Byrne, a consultant medical oncologist at St. James’s Hospital and a clinical professor at Trinity College, Dublin, Ireland. The FLEX trial was published before the EMEA decision, with investigators concluding that cetuximab can be considered as standard first-line therapy for all patients with advanced non-small cell lung cancer (NSCLC).

“Cetuximab is the first drug to show a survival benefit in all histological types: adenocarcinoma, squamous carcinoma – across the board. Secondly, the toxicities are all very predictable – we know how to manage them and they’re straightforward. Thirdly, not only was the FLEX trial positive but when you take in all the other trials together … as a collective they show a positive result,” said O’Byrne. He added that US National Comprehensive Cancer Network guidelines already recommend that the drug be considered for lung cancer patients, and that many oncologists in Europe have begun off-label usage.

O’Byrne acknowledged that cetuximab therapy would be costly, but noted that around half of patients display a strong predictive marker in the form of a skin rash, which develops after one round of chemotherapy. These patients tend to survive for around an extra 5 months, which may justify the cost, he said. More work is needed to confirm whether cetuximab offers any benefit for those who do not develop a rash, but it appears likely that therapy could be discontinued after one cycle in these patients, he said.

---------------------------------------------
*FLEX: First-Line Erbitux in Lung Cancer

Low-salt diet offers key to treating stubborn high blood pressure

Medical Tribune September 2009 P9

David Brill

Cutting down on salt can dramatically lower blood pressure (BP) in patients with resistant hypertension and could offer a genuine alternative to ramping up medications, a study suggests.

American researchers found that BP dropped by 22.7/9.1 mmHg after a week of a low-salt diet compared to a high-salt diet – a magnitude roughly equivalent to adding two more drugs.

This drop came on a background of heavy medication: patients in the study were already taking an average of 3.4 antihypertensive drugs per day.

Although small – just 12 patients took part – the study has been greeted enthusiastically by experts, who are calling for a renewed focus on salt reduction for patients whose BP remains uncontrolled.

Leading hypertension expert Dr. Lawrence Appel described the results as “striking,” particularly given that all study patients were taking hydrochlorothiazide. This volume-reducing therapy might have been expected to attenuate the effects of a low-salt diet, he wrote in an accompanying editorial. [Hypertension 2009 Jul 20; Epub ahead of print]

“The data presented … strongly suggest that persons with resistant hypertension are extremely sensitive to the BP-lowering effects of sodium reduction. The observed reductions in BP were huge – roughly equivalent to adding 2 antihypertensive medications,” wrote Appel, a Professor of Medicine at Johns Hopkins University, Baltimore, US.

“Although clinicians commonly focus on the next drug (e.g. aldosterone blocking therapy) and sometimes a device (e.g. Rheos systems that stimulate carotid baroreceptors), a renewed and aggressive emphasis on lifestyle modification, specifically sodium reduction, is warranted in patients with resistant hypertension and uncontrolled BP.”

Dr. Low Lip Ping, chairman emeritus of the Singapore Heart Foundation and founding president of the Singapore Hypertension Society, said: “This small but interesting study showed that among patients with medication-resistant hypertension, salt restriction has a substantial impact on lowering blood pressure by reducing intravascular fluid retention and improving vascular function.”

“Dietary salt restriction, ideally to less than 100 mEq of sodium/24 hours, should be recommended for all patients with resistant hypertension. With a low-salt diet these patients could have their blood pressure controlled with fewer medications,” said Low, also a private practitioner at the Low Cardiology Clinic, Mount Elizabeth Medical Center.

The study is the first to demonstrate that the benefits of salt reduction extend beyond patients with just mild or moderate hypertension, according to lead author Dr. Eduardo Pimenta.

“A low-salt diet is beneficial for all patients with hypertension but in patients with resistant hypertension the effect is stronger. Before prescribing another antihypertensive medication, doctors should spend more time with their patients explaining about low-salt diets and, if possible, refer the patient to a nutritionist,” said Pimenta, now a clinical research fellow at the Endocrine Hypertension Research Center, University of Queensland School of Medicine, Brisbane, Australia. The study itself was undertaken at the University of Alabama at Birmingham, US.

Study subjects had a mean office BP of 145.8/83.9 mmHg at baseline. All were randomized to either a high- or low-salt diet for 1 week, then a 2-week washout period, followed by a final week of the opposite diet. The low- and high-salt diets provided 50 and 250 mmol of sodium per day, respectively. [Hypertension 2009 Jul 20; Epub ahead of print]

All measures of BP were reduced by the low-salt diet as compared to the high-salt diet: systolic and diastolic; office and ambulatory; and daytime, nighttime and 24-hour.

The Singapore Heart Foundation and Hypertension Society have already been promoting the message about salt reduction – especially in light of National Nutrition Survey data suggesting that nine out of 10 Singaporeans exceed the recommended sodium intake of 2,000 mg/day.

In a joint statement to mark World Hypertension Day in May this year, the societies urged “all residents in Singapore to reduce their salt intake to reduce their risk of hypertension and hypertension-related diseases.” They also called on chefs and restaurants to lower the salt content of foods, and to avoid routinely providing soy sauce unless requested by the customer.

Cognitive rehab shows promise for stroke patients

Medical Tribune September 2009 SFI
David Brill

A cognitive rehabilitation program used after traumatic brain injuries could also help stroke patients to overcome lingering attention deficits, a new study shows.

Stroke survivors who received Attention Process Training (APT) within 4 weeks were better able to concentrate on visual and auditory tasks 6 months later, New Zealand researchers reported in the journal Stroke.

It is the first study to test APT in an important but neglected area of stroke rehabilitation, the researchers say. Concentration problems are very common in stroke patients – affecting quality of life and contributing to poor functional outcomes – yet specific interventions remain largely unstudied.

Singapore stroke expert Dr. Nagaendran Kandiah, a consultant neurologist at the National Neuroscience Institute (NNI), said that APT could be a useful tool for local patients but that equivalent programs would need to be tailored to the language and culture. Researchers at the NNI are already “actively working on this”, he said.

Further research is also needed to better establish the local prevalence of post-stroke attention deficits, he added. Preliminary data from NNI suggest that about 15 to 20 percent of patients have cognitive difficulties, including poor attention, following a stroke.

“There is a significant amount of literature that shows that cognitive training is useful for post-stroke patients. The awareness that attention deficits and other cognitive deficits are common and can be potentially treated needs to be emphasized both to the public and medical community,” said Nagaendran.

The Stroke study researchers randomized 78 stroke patients to receive standard care alone or standard care plus up to 30 hours of APT (mean 13.5 hours). [2009 Jul 23; Epub ahead of print]

APT patients scored significantly better on the Integrated Visual Auditory Continuous Performance Test (IVA-CPT) Full-Scale Attention Quotient (FSAQ), at 5 weeks and 6 months after randomization. The test measures reaction times to auditory and visual stimuli, and can distinguish between genuine attention to the task and impulsive responding.

There were however no significant differences between the groups in other cognitive performance indicators, or broader outcome measures such as the Physical Component Score.

Lead author Dr. Suzanne Barker-Collo, a clinical psychologist and senior lecturer at the University of Auckland, said that she was disappointed that the intervention did not show benefit across other domains but was pleasantly surprised at the magnitude of effect on the primary outcome.

“We were expecting maybe half a standard deviation difference between the groups, and the effect we found was about four times that,” she said.

There are several cognitive rehabilitation packages available but very little evidence on how best to use them in stroke patients, added Barker-Collo, whose ongoing research seeks to better delineate the profile and time course of cognitive deficits after stroke. She is also reviewing the data from the present study to identify factors that could predict which patients will respond best to APT.

“I think cognition after stroke in general has been ignored to some degree,” she said. “A lot of rehabilitation time is spent on more physical tasks like walking, bathing and dressing – it’s very practical but very often the time spent on that means that not as much time is spent on other things like attention and memory, which are a bit less obvious but can still impact on other functional outcomes. Attention deficit in particular is a very, very common problem.”

Questions raised over vertebroplasty for osteo fractures

Medical Tribune September 2009 P12
David Brill

Vertebroplasty performs no better than a placebo procedure for treating painful osteoporotic fractures, two major new studies have found.

Despite its widespread usage and recommendation in guidelines, vertebroplasty did not relieve pain, alleviate disability or improve quality of life compared to sham interventions, US and Australian researchers reported.

The studies are the first true randomized controlled trials to assess a procedure which has become a firmly established treatment for osteoporotic fractures. The number of vertebroplasties performed in the US, for example, almost doubled from 2001 to 2005. [JAMA 2007 Oct 17;298(15):1760-2]

The jury is still out as to how the findings will influence practice, according to an orthopedics expert whose editorial accompanies the papers in the New England Journal of Medicine. [2009 Aug 6;361(6):619-21]

“Although the trials by Kallmes et al. and Buchbinder et al. provide the best available scientific evidence for an informed choice, it remains to be seen whether there will be a paradigm shift in the treatment of vertebral compression fractures with vertebroplasty or similar procedures,” wrote Dr. James Weinstein, chair of the department of orthopedic surgery at Dartmouth-Hitchcock Medical Center, US.

Given the rise in the number of vertebroplasties and the questionable risk-benefit ratio, it is now essential that patients be well informed about the procedure, added Weinstein.

“When faced with several choices for which the evidence is less than clear, patients and doctors must thoroughly review the options together. Informed choice helps to educate patients about treatment options and allows them to recognize that a decision can be based on their values and preferences,” he wrote.

The larger of the two trials, led by Dr. David Kallmes of the Mayo Clinic, Rochester, US, followed 131 patients with osteoporotic vertebral compression fractures. They received either vertebroplasty or a simulation procedure in which cement was not injected into vertebrae. [N Engl J Med 2009;361:569-79.]

At 1 month there was no difference between groups on a pain scale ranking intensity from 0 to 10 (difference 0.7; 95% CI -0.3 to 1.7; P=0.19) or on the Roland-Morris Disability Questionnaire (difference 0.7; 95% CI -1.3 to 2.8; P=0.49). There was however a non-significant trend for more patients in the vertebroplasty group to report clinically meaningful improvements in pain (64 percent versus 48 percent; P=0.06).

Patients were subsequently allowed to cross over and receive the other intervention – still unaware of which they had already received. At 3 months, this option had been taken up by more control patients than vertebroplasty patients (43 percent versus 12 percent), but all patients who crossed over reported comparable or worse outcomes than those who received only the first intervention.

The second trial, led by Dr. Rachelle Buchbinder of Monash University, Australia, reported 6-month follow-up of 35 vertebroplasties and 36 placebo interventions. [N Engl J Med 2009 Aug 6;361(6):557-68]

Both interventions did relieve pain but to a comparable extent: at 3 months, the mean reductions (also measured on a 10-point scale) were 2.6 in the vertebroplasty group and 1.9 in the control group (adjusted between-group difference 0.6; 95% CI -0.7 to 1.8). This difference was also not significant at 1 week or 1 or 6 months; nor was there anything nothing to choose between groups on a range of secondary outcomes, including physical functioning and quality of life.

“It has been argued that performing a randomized, placebo-controlled trial of vertebroplasty is unnecessary and unethical in view of the published results of numerous studies that suggest a benefit of vertebroplasty. Our results show – not for the first time – the hazards of relying on the results of uncontrolled or poorly controlled studies to assess treatment efficacy,” the authors wrote.

Bacteria eradication holds hope for stomach cancer prevention

Medical Tribune September 2009 P14

David Brill

A new study has renewed hopes for reducing the incidence of gastric cancer – a leading cause of death worldwide and a particular burden for Asia.

The link between Helicobacter pylori infection and gastric cancer is well known, but Italian researchers now provide some of the strongest evidence yet that eradicating the bacteria can actually reduce cancer risk.

In a meta-analysis of data from 6,695 participants, they report that H. pylori eradication reduced the relative risk of gastric cancer to 0.65 (95 percent CI 0.43 – 0.98) over up to 10 years of follow-up. [Ann Intern Med 2009;151:121-8]

The findings lend support to a recent Asia-Pacific consensus statement calling for H. pylori screening and eradication in high-risk populations.

Japan and China have the world’s highest rates of gastric cancer, with age-standardized incidences of 62.1 and 41.4, respectively, per 100,000 males and 26.1 and 19.2 per 100,000 females. [CA Cancer J Clin 2005;55:74-108]

Dr. Lorenzo Fuccio, lead author of the meta-analysis, stressed that the cancer risk reduction with H. pylori eradication was only marginally significant, but could prove vital in countries such as these.

“Even a small reduction in risk and incidence achieved with H. pylori treatment will probably give a huge advantage in terms of social health, especially in high-risk areas,” said Fuccio, of the department of internal medicine and gastroenterology at the University of Bologna, Italy.

“Furthermore, H. pylori eradication provides several other benefits: it reduces the risk of peptic ulcer development, it can resolve dyspeptic symptoms and it can resolve gastritis. Once H. pylori is detected, especially in high-risk areas, eradication is always advisable.”

Asia-Pacific experts released their consensus statement on gastric cancer prevention last year, concluding that “there is a definite causal link between H. pylori infection and gastric cancer, and it has come time to try and intervene to prevent this cancer at the population level.” [J Gastroenterol Hepatol 2008;23:351-65]

Lead author Professor Fock Kwong Ming said that H. pylori screening and treatment should be a complement to, not a replacement for, existing cancer surveillance strategies in high-risk countries.

Research is still ongoing to establish exactly who to screen in intermediate-risk countries such as Singapore and Malaysia, said Fock, a senior consultant gastroenterologist at Changi General Hospital (CGH), Singapore. The highest-risk group in Singapore appears to be Chinese males aged 45 to 50, he said.

Previous work showed that gastric cancer risk correlated with H. pylori infection in Chinese and Malay individuals but not Indians. Gastric cancer rates are known to be lower in the latter two groups. [J Gastroenterol Hepatol 2005 Oct;20(10):1603-9]

Two studies are currently underway in Singapore to identify risk factors for gastric cancer development.

The first – a 5-year, S$25 million project conducted across several institutions in the Singapore Gastric Cancer Consortium – will correlate endoscopy and biopsy findings to gastric cancer outcomes, with a view to understanding how cancer develops and improving early detection rates. The second study takes place at CGH, and involves narrow-band endoscopy – a more specialized technique which may be better able to detect precancerous lesions.

Fuccio noted that randomized, multicenter trials are needed to fully understand the impact of H. pylori eradication on cancer prevention, but that such studies would present considerable ethical, logistical and financial challenges. Achieving statistical power would require thousands of participants and decades of follow-up, he said.

He added that gastric cancer results from a complex combination of genetic and environmental factors, and that eradicating H. pylori does not completely abolish risk.

H. pylori eradication is typically achieved using two antibiotics combined with a proton-pump inhibitor.

No benefit to excessive BP lowering, study says

Medical Tribune September 2009 P14
David Brill

Lower is not necessarily better when it comes to blood pressure (BP), a recent systematic review has found.

The analysis of seven randomized trials concluded that there was no clinical benefit to lowering BP beyond a currently recommended target of 140/90 to 160/100 mmHg.

Patients treated to lower targets did achieve significantly lower BPs (-4/-3 mmHg), but there were no differences in total mortality, major cardiovascular events, myocardial infarction or stroke rates compared to those treated to standard targets.

The review included data from a total of 22,089 patients, who had taken part in trials targeting various different diastolic BPs below 85 mmHg. No suitable trials of low systolic BP targets were identified. [Cochrane Database Syst Rev 2009;(3):CD004349]

“At present there is no evidence from randomized trials to support aiming for a BP target lower than 140/90 in the general population of patients with elevated blood pressure,” said lead author Dr. Jose Arguedas, of the University of Costa Rica, Costa Rica.

“Our research included patients with diabetes or chronic renal disease, and the evidence was slightly less robust for those subgroups of patients. We intend to carry out separate systematic reviews for those subgroups, especially because guidelines recommend even lower blood pressure targets for them,” he added.

There were also no significant differences in the incidence of congestive heart failure (relative risk [RR] 0.88, 95% CI 0.59 – 1.32) and end-stage renal disease (RR 1.01, 95% CI 0.81 – 1.27) between patients treated to low, as compared to standard, targets.

The full picture remains unclear with regard to safety, the authors note, since six of the seven trials did not provide complete information on serious adverse events and withdrawals.

Excessive BP lowering could cause unnecessary cost and inconvenience to patients, as well exposing them to a potential increased risk of adverse events if the number of antihypertensive medications is increased, they add.

Sunken treasure

Medical Tribune September 2009 P18
David Brill

If Subic Bay seems unremarkable you may be looking in the wrong place. David Brill finds that attraction lies beneath the surface.

Looking out over Subic Bay, you could be forgiven for thinking you’d booked the wrong trip. Tankers float out at sea, cranes loom over the shoreline, and litter washes up at your feet. Far from the glorious beaches of Boracay or Palawan, Subic does not at first glance appear an obvious destination for visitors to the Philippines.

A look below the water, however, tells a different story. An entire fleet of shipwrecks sits silently at the bottom of the sea, oblivious to the trivial goings-on at the surface. Anemones sprout on deck, while lionfish lurk in twisted metal crannies below. Barracudas swim down gun turrets, emerging in ghostly loading chambers long disused and overgrown with rust. Subic is a sunken goldmine – entry only for those with a diving license.

Back on land, Subic Bay was home to a US naval base until forces withdrew in 1992. The area of the base remains enclosed as the Subic Bay Freeport Zone – the shipyards making way for hotels, restaurants and casinos. International access is via Clark airport, some 2 hours drive southeast of Subic, or from Manila, a further 3 or so hours south of Clark, depending on traffic.

Some of Subic’s shipwrecks date back to the Spanish-American war of 1898, but the majority sank during the years of World War II. Twenty-five ships from Japan alone are claimed to have gone down during the war but with salvage operations undertaken in the 1950s, no one is quite sure how many wrecks remain in the bay. Best guesses suggest that there are some 20 wrecks in still waters – 10 or so of which are suitable for recreational diving.

The main attraction at Subic Bay is the USS New York. Launched in 1891, she played a key role in the Spanish-American war before returning to action in World War I as the USS Saratoga. She was eventually decommissioned in the Philippines in the 1930s and remained moored at Subic Bay until 1941, when she was deliberately scuttled by retreating US forces to prevent her from falling into the hands of the Japanese.

The navy’s loss proved to be scuba divers’ gain, as the 120-meter-long USS New York came to rest on its side with its topmost point just 17 meters from the surface. This depth leaves the top of the wreck accessible for novice divers, with the inside and lower decks offering a variety of options for those seeking more challenging, technical dives. The engine rooms lie at the very bottom of the ship and remain largely unexplored.

Visibility was mediocre during a trip in late July but the wreck is eerily impressive nonetheless. Its sheer, hulking size is enough to leave you feeling insignificant by comparison, while the sight of its three giant gun barrels emerging ominously from the gloom offers another reminder of the vast power the ship once wielded. A variety of wildlife circulates the site: dive instructors list barracuda, rays, octopi, lobsters and spotted sweetlips among the wreck’s inhabitants, although not all were seen on our trip.

Other wrecks at Subic Bay include El Capitan, a shallow site which is easily accessible for all comers. Even fairly novice divers can swim through the hold, and poke their head up into a pocket of trapped, ancient air (attempting to breathe it is strongly not advised). Also of note is the infamous Oryoku Maru – a Japanese cruise liner used for transportation of prisoners of war from Manila to Japan. Later dubbed ‘The Hell Ship’ for the nightmarish conditions in which prisoners were kept, she was bombed and sunk at Subic by US navy planes in 1944. Several other vessels are accessible – including a largely intact Japanese patrol boat – along with various sites of debris, scattered metal, and even a few coral reefs.

Beyond the diving, a few activities are available at Subic, including horse riding, watersports, go-karting and, of course, gambling. Much of the area, however, feels run-down and seedy, and considerable regeneration will likely be needed if tourists are to come in large numbers. In the meantime, however, Subic offers an enjoyable and convenient weekend for divers, especially given the proximity of the wrecks to the shore and the relative ease of transport from abroad. Don’t be fooled by the cranes and tankers – Subic Bay is to be judged on what lies below.