Outcome studies for cardiac imaging needed

Medical Tribune June 2008 P1
David Brill

Doctors should wait for more clinical data before adopting the latest cardiac imaging techniques, according to a specialist.

“The technology is far outpacing the evidence, so what’s happening is that people are actually moving on to the next technique without properly evaluating the previous technique,” said Dr. Joseph Selvanayagam, a cardiologist at the Flinders Medical Center in Adelaide, Australia.

“What these modalities really need to work on is not necessarily to keep improving the technology … but to invest in clinical outcome studies that look at whether doing these tests in patients actually improves outcomes and reduces cost. Otherwise we will be criticized for purely being focused on the newest toy and not being focused on what’s actually best for the patient,” he said. “This is a real risk for everybody in this field.”

Speaking at the second congress of the Asian Society of Cardiovascular Imaging in Singapore, Selvanayagam told Medical Tribune that computed tomography (CT) is one such imaging modality where more clinical data is required.

“There are people who have become radical and are proposing [scanning] asymptomatic patients for indications which really there has not been data for. It’s something that we have to be careful of, particularly given that it’s a technique that has radiation and safety concerns,” he said.

Selvanayagam also addressed the role of cardiac magnetic resonance (CMR) as an initial test for assessing patients who present with acute cardiac disease – an application that is currently limited to a few high-volume centers owing to a lack of availability of scanners and concerns over the difficulties of monitoring and resuscitating patients during a scan. The relatively slow scanning speed of CMR is also problematic as patients are required to hold their breath, which can exclude those with chest pain.

Provided the patient is stable, however, CMR could become a routine first-line diagnostic test in suspected cases of cardiomyopathy, coronary artery disease and myocarditis, according to Selvanayagam. The versatility, high spatial resolution and three-dimensional nature of the technique offers an assessment of cardiac function beyond that which is possible with less specific tests such as electrocardiography, and can thereby assist with the diagnosis and triage
of these patients.

“I think in selected patients it will become a preferred technique,” he concluded. “I would encourage more centers to get adequate experience and training in CMR and once they have that, then to utilize it for these indications.”

Sharing decisions increases patient satisfaction

Medical Tribune June 2008 P4
David Brill

A simple system that promotes shared decisionmaking has been shown to improve patient satisfaction without affecting their cardiovascular risk.

Patients whose physicians adopted the system during an initial consultation also participated more in the decision-making process and expressed less decisional regret 6 months later.

“It seems they think their doctor takes their problems more seriously,” said Dr. Tanya Krones
from Phillips-University Marburg in Germany, lead researcher of a randomized controlled trial which tested the decision aid in 1,132 patients.

“We were really astonished that from just one consultation shaped in this way, we saw this big difference,” she added.

The system, known as ARRIBAHerz, has already been adopted in some parts of Germany. Krones estimates that around 1,000 physicians have begun to implement the decision aid into practice since the trial was completed.

Participating doctors were trained to follow a script of six decision-making steps which included
calculating and explaining the patient’s risk, addressing their expectations and agreeing on a course of action. Additional materials were also introduced into practice, such as summary sheets for the patient which depicted their individual risk using smiley faces.

Patient satisfaction was assessed directly after consultation using the Patient Participation Scale. The difference in score between the groups was .8 (P<.001). At 6 month follow-up the mean decrease in cardiovascular risk, as calculated using the Framingham system, was three percent for the intervention group and 3.33 percent for the control group (P=.31). Nineteen intervention patients (3.5 percent) and 22 control patients (3.7 percent) experienced a severe cardiovascular event during this period. Krones noted that some doctors were initially reluctant to use the system in high-risk patients, as providing decision-making authority to these patients could result in them making irrational choices and ultimately straying from the guidelines. The comparable decrease in risk suggests that this was not the case, she said, but she acknowledged the need for longer term follow-up. Previous decision aids have tended to focus on providing information for patients to read in their own time rather than attempting to influence the behavior of physicians during consultations, added Krones. ARRIBA-Herz was developed over 3 years in consultation with more than 200 family physicians. The results of the trial were published in The Annals of Family Medicine.

Islet transplantation needs further research

Medical Tribune June 2008 P7

David Brill

Islet transplantation is a promising technique for treating diabetic patients but the field still faces many unresolved issues, according to an expert.

“We can clearly state that a successful islet transplant can potentially provide insulin independence and halt long-term diabetic complications,” said Dr. Paolo Fiorina of Harvard Medical School, Boston, US, and the San Raffaele Scientific Institute in Milan, Italy.

Reviewing registry data from 7 years of transplants, he said that insulin independence can be achieved in 70 to 80 percent of patients who receive an infusion of islets. He added that the procedure is relatively easy to perform, is associated with short hospital stays and, when successful, can reduce the occurrence of hypoglycemic episodes.

Fiorina also highlighted studies which demonstrated that islet transplantation can improve cardiac and endothelial function and reduce cardiovascular mortality in type 1 diabetic patients. Successful islet transplantation can also improve graft survival and function among patients
who have received a kidney transplant, he said.

He concluded, however, that further study is required before the technique can be declared superior to insulin pumps or pancreas transplantation.

The safety of islet transplantation, for example, remains to be confirmed. Transaminitis occurs in half of patients, while 10 to 15 percent experience bleeding and five percent develop thrombosis. Longer-term complications include hyperlipidemia, hypertension, mouth ulcers
and an increased risk of sensitization and infection.

More research is also needed to improve procedural success rates, according to Fiorina.

“We still don’t know why islets fail,” he said, suggesting that graft rejection, insulin resistance and poor graft quality could all be important factors.

“All together, these problems make islet transplantation hard work,” said Fiorina.

The need for lifelong immunosuppression is another concern facing islet transplantation patients. This treatment can cause nephrotoxicity, and researchers have noted a decrease in kidney function 3 years after the procedure, as measured by glomerular filtration rate.

Reducing the toxicity of immunosuppression could help to improve the success of islet transplantation, according to Fiorina. He described this area of research as “an exciting and growing field.”

Islet transplantation was first performed in 1999. By 2007, 579 procedures had been documented in the Cell Transplant Islet Registry, most of them performed in North America and Europe.

Seasonal influenza originates from South-East Asia

Medical Tribune June 2008 SF I

David Brill

Seasonal influenza epidemics appear to emerge in East and South East (E-SE) Asia before spreading actross the globe, according to new research which could lead to improvements in future vaccine selection.

Scientists from the World Health Organization’s (WHO) Global Influenza Surveillance
Network used a technique called antigenic cartography to analyze the hemagglutinin component of some 13,000 human influenza A (H3N2) viruses that had appeared across six continents from 2002 to 2007.

“We were able to identify different strains of H3N2 as they arrived at new locations around the world over the 5 year study period,” said Colin Russell of the University of Cambridge, UK – lead author of the study.

“And we found solid evidence that each year since 2002, H3N2 viruses had migrated out of what we call the East and South East Asian Circulation Network.”

Influenza viruses are thought to be responsible for some half-a-million deaths worldwide each year. The WHO convenes twice annually to decide which particular strains to put into the latest influenza vaccines, but it can take up to 12 months to manufacture the 300 million doses required.

The research, published in the journal Science, found that once viruses leave E-SE Asia they typically take around 6 to 9 months to appear in Europe and North America, and do not subsequently reappear in Asia. Studying viral evolution patterns in S-SE Asia could therefore help to forecast which strains are going to reach the northern hemisphere the following year –
facilitating the strain selection process and leading to more effective vaccines.

Associate Professor Leo Yee Sin, clinical director of the communicable disease centre
at Tan Tock Seng Hospital, Singapore, commented that: “The findings presented in this study are of great interest to the world.

“It is an interesting notion that the E-SE Asia region can serve to predict likely circulating
strains. It is important to monitor the trend of influenza in this region and to prospectively validate the findings of this study,” she added.

According to the researchers there is not one particular place in E-SE Asia where new influenza strains evolve. It appears rather that viruses continually circulate within this regional network, giving rise to overlapping epidemics – the timing of which are driven primarily by climatic factors.

Oceania appears to be the first stop for H3N2 viruses leaving E-SE Asia, followed by Europe and North America. Viruses do not typically reach South America for a further 6 to 9 months – a delay that could be explained by the lack of direct travel and trade routes with Asia, the researchers suggest.

Vincent Chow, associate professor in the department of microbiology at the National University of Singapore, called the study a “landmark document.”

“It is an excellent model for global influenza monitoring … and represents a scientifically
sound basis for determining health and vaccine policy decisions in the future,” he said.

“Having the highest concentration of mega cities, Asia is an ideal melting pot for influenza viruses to spread, replicate and mutate,” added Chow.

More research needed into infant probiotics

Medical Tribune June 2008 SF7

David Brill

Probiotic drinks could help to stimulate the development of a newborn baby’s immune system but more research is required to fully understand their effects, a leading pediatrician has advised.

After birth, the immature gut is rapidly colonized by millions of different bacteria. The composition of this new ecosystem only becomes fixed after around 6 months – offering a window in which a baby’s immunological development could, theoretically, be influenced.

Whether this effect can be achieved by giving probiotic bacteria to infants is not yet clear, according to Bengt Björkstén, professor emeritus of pediatrics and allergy prevention at the Karolinska Institutet, Sweden.

“I think that’s the future. I don’t think we are there yet,” he explained, speaking ahead of the first regional Nestle Nutrition Institute Symposium, held last month in Singapore. “We need to learn more about the colonization process and which [bacteria] are truly beneficial and which are less beneficial.”

In the absence of this evidence, Björkstén believes that mothers should make their own decisions as to whether to give probiotics to their infants. “But I can honestly say
that I don’t see any downside,” he added.

Björkstén also stressed that consumers should be wary when buying probiotic drinks, as many contain bacteria for which there is no documented health benefit. Only three strains of lactobacillus (L. plantarum, L. reuteri and L. rhamnosus GG) and certain strains of bifidobacteria (particularly BB12) appear to be beneficial, he said.

These sentiments were echoed by Dr. Patricia Conway from the School of Biotechnology and Biomolecular Science at the University of New South Wales, Australia.

“Choose the probiotic wisely. Look for the strain identifier,” she advised. “If it does specify which one it is, the consumer can go on Google and find out what evidence there is for that particular strain.”

Probiotics could prove to be of particular benefit to babies born by cesarean section and those who are not breastfed, as they receive less exposure to maternal bacteria during their first months. Research has shown that even at 1 month of age, these babies have less so-called “good bacteria” and more “bad bacteria” in the gut than those who were born vaginally and breastfed.
[Pediatrics 2006 Aug;118(2):511-21]

Cesarean-born babies also appear to have a slight but significantly increased risk for allergies, according to Björkstén, although it remains theoretical as to whether this results from differences in gut microbial profiles.

“It is a hypothesis but it’s a reasonable hypothesis,” he concluded.

Disturbed sleep in Alzheimer’s not helped by medication

Medical Tribune June 2008 P1

David Brill

Sleep medications are not necessarily beneficial for Alzheimer’s disease (AD) patients, a study has shown.

Researchers from the University of Washington found that AD patients who used medications were six times more likely to experience poor sleep than those who did not.

Moreover patient medication use was associated with situations where their coresident family caregiver was also sleeping poorly, suggesting that the use of such therapies may not benefit either party.

Dr. Joshua Kua, deputy chief of the department of geriatric psychiatry at the Institute of Mental Health, Singapore, advised physicians who are dealing with AD patients to carefully assess all of the factors that might contribute to sleep disturbances before deciding on the appropriate treatment.

“Medication itself may not always be the solution or the panacea to sleep problems for a person with dementia or their caregiver. Try to think about a nonpharmacological approach first, rather than dishing out medication,” he said, adding that medication use can also worsen cognition levels and increase the risk of falls and fractures.

The researchers also found that patient depression is a significant predictor of poor sleep for both patients and caregivers. This is a factor that doctors need to be aware of when dealing with AD patients in future, according to Kua.

“Someone who is (suffering from dementia may not) be able to verbalize their feelings so the need to recognize depression – especially in advanced disease where language may be impaired – is very important. It’s something that we often miss, particularly in the primary care setting,” he said.

Sleep disturbances in dementia patients can place stress upon co-habiting caregivers, leading to tiredness and frustration. These feelings can increase the risk of the patient being institutionalized and in some cases may lead to elder abuse, according to Kua.

Dr. Lim Li Ling, medical director of the Singapore Neurology and Sleep Centre, added that a lack of sleep can lead to a further decline in cognitive function among dementia patients.

“Caregivers should know the importance of good quality and adequate sleep for both themselves and their charges,” she said.

Lim advised caregivers to develop regular sleep-wake schedules, avoid stimulants such as coffee or tea in the evenings, and to get regular exercise where possible. She added that patients should be given adequate daytime exposure to light in order to regulate their circadian clocks, and be kept occupied during the day in order to avoid excessive napping.

The study, published in the journal Sleep, comprised 44 patient-caregiver pairings whose sleep patterns were monitored over 1 week using wrist movement recorders. Other outcomes were assessed using a variety of tests, including the Cornell Scale for Depression in Dementia and the Dementia Management Strategies Scale.

Acknowledging the small size of the study, the researchers reported that larger scale investigations have already been initiated in order to better understand the factors that contribute to sleep disturbances in AD.

“Identifying common patterns and causes of sleep disturbances would … improve quality of life and overall physical and emotional wellbeing of both patients and caregivers,” added Lim.

ONTARGET results a boon to Asian patients

Medical Tribune June 2008 SFXV

David Brill

The results of the ONTARGET trial should give doctors more confidence in prescribing angiotensin receptor blockers (ARBs) to patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors – something that is more common among Asian patients, according to a Singapore cardiologist.

One study of 111 patients found ACE inhibitor intolerance among Chinese patients to be as high as 53 percent, whereas the incidence appears to be lower among Caucasian patients.[Am J Cardio 1995 May 1;75(14):967-8]

The reasons for this discrepancy are currently unknown, according to Dr. Bernard Kwok, senior consultant at the National Heart Centre, Singapore and one of the ONTARGET investigators in the region. He speculates that it could result from genetic differences.

Around 33 percent of heart failure patients at Kwok’s center develop cough in response to ACE inhibitor therapy, although this reaction usually disappears within 2 weeks of switching to an ARB. However, until recently, there was a lack of data to support the use of ARBs as an alternative for these patients.

“Finally, ONTARGET tells us that this is the correct thing to do and, more importantly, it tells us that telmisartan should be the preferred ARB in this case,” said Kwok.

The trial found that telmisartan was non-inferior to the ACE inhibitor ramipril in reducing cardiovascular events among high-risk patients without heart failure. Some 4,000 of the study’s 25,620 subjects came from Asian countries, including China, Singapore and Malaysia.

“The patients who were studied in ONTARGET … are very representative of the type of patients that we see on a daily basis,” said Kwok.

“We can no longer say ‘oh this study was done in Americans or Europeans so the results may not apply to Asians.’ These results should apply globally.”

The study also demonstrated that telmisartan was better tolerated than ramipril. The drug was associated with significantly lower rates of cough (1.1 percent compared to 4.2 percent) – the most common side effect of ACE inhibitors – and angioedema (.1 percent compared to .3 percent).

Despite these findings Kwok does not believe that ARBs should become first-line therapy for all cardiac patients, owing to the greater cost-effectiveness of ACE inhibitors. ARBs should be reserved for those who cannot take ACE inhibitors, he said.

The results of ONTARGET were presented earlier this year at the annual meeting of the American College of Cardiology and subsequently published in the New England Journal of Medicine. The efficacy of ARBs had been previously documented in subgroups of patients such as those with heart failure and hypertension, but had not been established in the broader-
risk population included in the study.

Future trials are likely to assess the role of ARBs in other subgroups such as patients who have
had a myocardial infarction, said Kwok.