The benefits of combining women’s and children’s healthcare

Medical Tribune August 2008 P2-3

Associate Professor Tay Eng-Hseon reflects on the advantages offered by centers such as KK Women’s and Children’s Hospital, Singapore

A mother and her child share a special relationship that begins even before birth. Having a combined hospital to attend to both of their needs provides continuity of care for the new family, and can help to develop and strengthen this bond. The ability to deliver specialist pediatric care on-site removes the potential need to separate a mother from her newborn baby within moments of delivery, enabling the family unit to remain intact within the same hospital. And as the child continues to grow, mothers can enjoy the convenience of having their own health needs attended to at the same place as those of their children. Joint visits such as this can help to reinforce the social support network and cohesion within a family.

Combining women’s and children’s healthcare is also beneficial from a medical standpoint as well as a social one. Delivery of crossover services becomes quicker, easier and more efficient within a single site. Many times at KK Women’s and Children’s Hospital (KKH) we have witnessed a neonatologist supervise the birth of a child before handing over to the pediatric urologist or cardiac surgeon, thereby allowing treatment to continue promptly without interruption or the need for further travel, with the associated delays and costs that this entails.

KKH treats a more specific section of the community than a general hospital, and this has proved to be beneficial from a practical point of view as well. With the field of potential patients narrowed we can reduce the range of equipment that we need, keep a more specific selection of drugs at the pharmacy, and standardize the hospital wards to a greater degree. We can also provide more specialized training for physicians, who can gain hands-on experience of a wide spectrum of conditions within their discipline.

Specializing in this way also has benefits for research, enabling a greater focus which in turn improves the ease of execution. Consequently KKH has participated in several large-scale international trials, including those of the rotavirus and cervical cancer vaccines. Entry into trials such as these can be competitive, but the ability to accrue large numbers of subjects quickly and easily has enabled our hospital to stay ahead of the competition. Furthermore we can provide a different patient perspective to centers in Europe and the US, and for these particular studies KKH was the main provider of Asian subjects.

Until 1997, pediatric hospital care in Singapore was spread between Tan Tock Seng, Singapore General and National University Hospitals. The visionary decision to consolidate these services into KKH – previously a dedicated women’s hospital – has enabled the hospital to expand into new areas and provide further dimensions of care to its patients. Examples include the development of highly specialized breast surgery and plastic and reconstructive surgery teams, and the opening of the Women Wellness Centre and Department of Child Development. Promoting mental health within the same vicinity as physical health also has the added benefit of reducing the stigma that can be associated with conventional psychiatric settings.

In a large specialist center such as KKH, the progression to higher-level services is a natural one, and it would not be surprising to see the private sector develop along these lines in future. High-end secondary and tertiary care such as this can only be feasible when there is access to a high volume of primary care patients, however, otherwise the demand will not match the capacity for supply and an expensive excess will develop.

In Singapore, patients from all corners of the country can reach the hospital within 30 minutes, making the concentration of care into one specialist centre very feasible. By virtue of its size and position within a dense population, KKH delivers a third of the 38,000-odd babies born each year in Singapore and provides care for around 80 percent of the country’s children. This model of centralized combined healthcare might not be feasible in all countries, however, and smaller hospitals in more sparsely-populated areas may not be able to match the volume of patients needed to sustain a dedicated center.

By focusing and centralizing our services we have been able to enhance our international reputation and provide regional leadership, and over the years we have attracted many foreign doctors on training fellowships. Other countries have begun looking into our model of hospital structure, and there has been a lot of interest from China in particular. For now women’s and children’s hospitals remain a rarity within Asia but, as KKH demonstrates, this system can provide many important benefits to both doctors and patients at all levels of care.

Laquinimod shows promise for multiple sclerosis

Medical Tribune August 2008 P3

The novel immunomodulatory agent laquinimod appears to reduce disease activity in relapsing-remitting multiple sclerosis and could be a promising new treatment for the condition.

A randomized phase IIb trial involving 306 patients found that, compared to patients who took placebo, those who took oral laquinimod (.6 mg daily) had a 40.4 percent reduction in the number of gadolinium enhancing lesions seen on magnetic resonance imaging at weeks 24, 28, 32 and 36. The drug was well tolerated, with a similar adverse event rate to placebo.

The drug is due to undergo further assessment in a phase III clinical trial.

[Lancet 2008 Jun 21;371(9630):2085-92]

Nanotubes can be used to ‘cook’ tumor cells

Medical Tribune August 2008 P3

Cancer cells can be killed using nanotechnology to deliver a highly specific heat source, a study has shown.

Researchers at the University of Texas Southwestern Medical Center, US, coupled single-walled carbon nanotubes to monoclonal antibodies and targeted these to lymphoma cells in vitro. Exposure to near-infrared light caused the nanotubes to emit heat, thereby ablating the tumor cells while leaving other cells unaffected.

Describing the specificity of the technique as “excellent”, the researchers conclude that the next step is to evaluate the use of these nanotube-antibody constructs in vitro.

[Proc Natl Acad Sci U S A 2008 Jun 24;105(25):8697-702]

New type of cardiac stem cell discovered

Medical Tribune August 2008 P3

Scientists at Harvard have identified a new type of precursor cell which develop into cardiomyocytes.

The cells are located in the epicardium and can be identified through their expression of the Wt1 gene, the researchers reported in Nature. A subset of these cells gave rise to fully functioning cardiomyocytes during normal development of the mouse heart. Other epicardial cells had been previously shown to differentiate into endothelial and smooth muscle cells but not cardiomyocytes.

Identifying these progenitor cells could enable future research to harness their potential for cardiac repair and regeneration, the study authors conclude.

[Nature 2008 Jun 22. Epub ahead of print]

Heel ultrasound predicts osteoporotic fracture risk

Medical Tribune August 2008 P5
David Brill

A simple formula combining clinical information with quantitative ultrasound data from the heel can be used to predict whether a woman is at risk for osteoporotic fractures, a study has shown.

The prediction rule, which assigns patients a risk score from 0 to 14, was tested in 6,174 Swiss women aged 70 to 85 who were followed up for 2.8 years.

Rates of osteoporotic fracture were 6.1 percent among women defined as high-risk and 1.8 for those defined as low-risk, when using a cut-off score of 4.5. The sensitivity of the formula using this score was 90 percent.

“The whole idea of this study was to end up with a tool that can be used by primary care physicians on a daily basis,” said Dr. Idris Guessous, lead author of the study which was published in Radiology.

Ultrasound is inexpensive and portable, he added, and could be used as a diagnostic screening tool in countries where costly bone mineral density (BMD) scans are not available. Resource-permitting, the two modalities could be used in combination for select high-risk women he said.

Dr. Lau Tang Ching – consultant rheumatologist at Tan Tock Seng Hospital, Singapore – said that ultrasound could be useful for assessing nursing home patients who would have difficulty visiting hospital for a BMD scan.

He added, however, that he would like to have seen the authors report the continuous score spectrum for fracture risk prediction, rather than using the single cut-off point of 4.5.

“It would also be good if the test characteristics of the ultrasound machine were compared with dual X-ray absorptiometry BMD or with other well established predictors of low BMD such as the Osteoporosis Self-Assessment Test,” said Lau.

The researchers used a quantitative ultrasound device which requires an operator to position the subject’s foot in a water bath. The measurement procedure is otherwise automatic.

“What is really specific to this study is the way that clinical risk factors – history of fractures or recent fall – are combined with this ultrasound technique, so there are two domains that are included in the score,” said Guessous, who is a senior research fellow at Lausanne University Hospital in Switzerland.

“I stress this point because this score may not only highlight the quality of the bone itself, which is a major risk factor for fractures, but it also highlights the risk of fall for a woman.

“Depending on which factors the woman is at risk for you may better target your intervention, so eventually women who are at more risk of falling than having a bad quality of bone may end up having other interventions like hip protectors or rebalancing techniques, than just receiving bisphosphonate drugs,” he said.

Healthcare systems urged to vaccinate workers

Medical Tribune August 2008 P7
David Brill

Widespread vaccination programs should be introduced for all healthcare workers and backed by the WHO, according to an infectious diseases expert from Mexico City.

Describing healthcare as “a very risky activity,” Dr. Samuel Ponce de Leon told the ICID that death and disease among personnel can have serious consequences for systems that are already short of important resources.

“Healthcare workers are an endangered species and a very reluctant one to be protected. A total of 57 countries, mostly in sub-Saharan Africa but also some Asian countries, face crippling healthcare worker shortages.

“Every health system, hospital, institute and outpatient clinic, private or public, should establish a program to vaccinate all healthcare workers as part of a comprehensive healthcare program,” he said, adding that “the WHO should establish obligatory regulation to protect healthcare workers.”

Hepatitis B, influenza, measles, rubella, tetanus and diphtheria – just some of the diseases faced by healthcare workers – should form the very minimum components of vaccination programs, according to Ponce de Leon.

Workers risk catching a wide range of infectious diseases from their patients if they are not vaccinated, and can be responsible for passing these on to other patients, medics and the community at large.

Compliance to healthcare worker vaccination schemes is typically poor, he said, suggesting that poor communication and lack of knowledge are typically responsible. Workers may also be reluctant to give up their time, have a fear of needles, or perceive vaccination as dangerous or unnecessary.

“Healthcare workers should be clear that compliance to be vaccinated is an ethical duty,” he said.

Despite the obstacles, vaccine uptake can be successfully promoted said Ponce de Leon, citing the example of a hospital campaign in Korea which boosted influenza vaccination rates among workers from 27 to 52 percent. [Infect Control Hosp Epidemiol 2006 Jun;27(6):612-7]

Beyond the basic schedule, vaccination programs could be extended to include hepatitis A, varicella and pneumoccocus, he said.

He added that avian influenza is also an area to consider but several issues remain unresolved as to what the best vaccine is and when best to use it.

Hygiene and education key to reducing catheter-related infections

Medical Tribune August 2008 P7
David Brill

Some 250,000 catheter-related bloodstream infections (BSIs) occur each year in the US, with mortality as high as 35 percent and avoidable costs totaling around US$6.25 billion.
Pic: hospital patient with a catheter line

However the number of infections can be dramatically reduced by following a range of simple steps, according to Trish Perl who is Professor of medicine, pathology and epidemiology at Johns Hopkins Hospital (JHH) in Baltimore.

Since introducing measures to reduce the rates of catheter-related BSIs, JHH has seen a 75 percent decrease across all of their adult intensive care units in the past 6 years, she said. The hospital published a report in 2004 in which they estimate that 43 BSIs, 8 deaths and nearly US$2 million dollars in costs have been prevented each year by the intervention strategy. [Crit Care Med 2004 Oct;32(10):2014-20]

Perl outlined three major contamination sites that can cause BSIs: the skin and insertion site, the catheter hub and the infusate. Each of these points provides a focal target for prevention strategies, she said, noting that the former two are of the greatest concern in developed countries whereas the latter is more of a problem in the developing world.

“It remains important to cleanse your hands … that recommendation actually has the strongest evidence,” said Perl, adding that employing maximal barrier precautions and educating health care workers who place catheters can also help to avoid skin-derived infections.

“These three recommendations are highly, highly supported by the evidence and should be in place in all settings. Knowledge and adherence to guidelines for all persons placing lines has also been shown to decrease your BSI rates,” she said.

Suggested maximal barrier precautions include wearing sterile gloves and gowns and tight-fitting non-sterile masks and hats, and covering the patient’s body with a sterile drape. Consideration should also be given to the site of catheter insertion, as the subclavian vein is associated with lower infection rates than the internal jugular and femoral veins she said.

Beyond the insertion site, catheter hubs and infusates are also an important source of infections said Perl, citing a study of four pediatric hospitals in Mexico City which found that 70 percent of injection ports and 7 percent of infusates were contaminated. [Infect Control Hosp Epidemiol 2004 Mar;25(3):226-30]

“Coated catheters have been shown to decrease BSI rates but given the cost we need to determine the high-risk patients and ensure that other prevention strategies are in place,” she said, adding that the use of antiseptic ports and caps and new stopcock models seem to cut infection rates.

BSI rates also seem to increase when nursing staff levels are low, and ensuring adequate levels of care at all times may also be an important prevention strategy.

Perl noted, however, that certain newer models of needleless connectors have actually led to increased infection rates.

“I think we have to really start considering whether or not the technology can actually contribute to BSIs,” she said.

Perl concluded by adding that future infection control programs should use standard definitions, so that feedback can be easily provided to the healthcare workers who are responsible for the placement of catheters.

Community-acquired MRSA: The new breed of nosocomial pathogen

Medical Tribune August 2008 P9
David Brill

The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as a nosocomial pathogen presents a range of new challenges for both prevention and management, according to a leading infectious disease specialist.

Professor Richard Wenzel, president of the International Society for Infectious Diseases, told the audience at the ICID that CA-MRSA appears to be more virulent than other nosocomial strains and has an unknown epidemiology.

He described the case that first “gave him respect for CA-MRSA:” a 22-year old male who deteriorated rapidly and died within 36 hours.

The patient had normal heart sounds on admission, yet developed a systolic murmur and symptoms of endocarditis after 16 hours. CT at presentation was also normal, yet MRI performed shortly before death showed around 100 brain abscesses which were later confirmed by biopsy.

It is unclear exactly what makes CA-MRSA so virulent, said Wenzel. The Panton-Valentine leucocidin (PVL) gene and alpha hemolysin have both been implicated in animal models, but their precise roles remain unclearly defined.

Screening also appears to be a complicated issue: a prospective cohort study of 51 CA-MRSA patients found that only 41 percent were nasal carriers, while a report of five patients who received the infection via heterosexual transmission revealed that only one was a nasal carrier.

Screening would therefore underestimate the prevalence of the USA-300 and USA-400 strains, Wenzel said, whereas in cases of nosocomial MRSA the majority of patients test positive for USA-100.

“This is important because people in the US are saying we just have to screen people so we know who’s out there. But it’s not that simple,” he said.

The antiobiogram for CA-MRSA also seems to differ from other types of infection, and the optimal treatment strategy remains unclear.

“The problem is what drugs do you use? I want to tell you this is getting complicated,” said Wenzel, who is chairman of the department of internal medicine at Virginia Commonwealth University, US.

“For life-threatening infections, antibiotics that inhibit protein synthesis and intravenous immunoglobulin may be useful,” he said, but noted that side effects are an issue with many of the available drug treatments.

“Linezolid we think is a relatively good drug but neuropathy, lactic acidosis and serotonin syndrome have all been described.

“Daptomycin looks good in comparative trials for skin and soft tissue. However, it’s not recommended for pneumonia because surfactant inhibits the antibacterial activity.”

He added that vancomycin can lead to renal failure when given with amino glycosides, while trimethoprim causes hyperkalemia in the majority of patients.

Definitive answers are still lacking on what treatments to use either for preventative prophylaxis of CA-MRSA or for treating ventilator-associated pneumonia, Wenzel said, noting that there are currently no clinical trials which can inform these decisions.

Improving our knowledge of resistant pathogens, drug interactions and the adverse events of antibiotics may help in future, he said.

“The plans for changing the prophylactic and empirical therapy for nosocomial infections need to begin right now,” he concluded.

Family-based approach improves CVD prevention

Medical Tribune August 2008 P10
David Brill

Standards of cardiovascular disease prevention in primary care can be improved by implementing a multidisciplinary family-based programme, an international study published in The Lancet has shown.

Patients who took part in the EUROACTION trial – the largest research project ever carried out by the European Society of Cardiology – demonstrated improvements in their diet, physical activity levels and smoking status a year later.

They were also more likely to have better control of cholesterol levels and to achieve blood pressure targets, without an increase in the use of antihypertensive drugs.

Many of the healthy lifestyle changes achieved by the patients extended to their partners, who were also targeted by the programme.

The active involvement of family members in EUROACTION is a big step forward for preventive cardiology, according to Professor David Wood of Imperial College London, who led the study.

“Often the person responsible for the shopping and cooking is not the patient so to make dietary changes they need to be made in the family as a whole. And that’s what we achieved – we saw the same direct changes in the partners as in the patients,” he said, adding that similar family-wide effects were observed for smoking and physical activity.

Dr. Shyamala Thilagaratnam from the Health Promotion Board in Singapore said that: “The results indicate very encouraging effects of an intensive intervention programme for cardiovascular disease prevention.

“A supportive home environment is an important determinant of successful lifestyle behavioural modification,” she said, adding that a similar approach to that seen in the study could be considered for local programmes.

EUROACTION was conducted across 8 European countries with a range of different health economies.

“We were able to fit in with whatever was available on the ground, which means that our programme could be implemented in any comparable healthcare setting,” said Wood.

He added that the trial was intentionally carried out in “hard-working” hospitals and general practices in order to ensure that the results were generalizable.

EUROACTION involved 2,317 patients recruited from general practices who were asymptomatic but at high-risk for developing cardiovascular disease, and 3,088 hospital patients with established coronary heart disease. [Lancet 2008 Jun 14;371:1999-2012]

Each group was randomized to receive usual care or participate in the study intervention, which involved an initial assessment and regular follow-up meetings with a dietician, a physiotherapist and a specially-trained nurse. Patients and their partners were encouraged to work towards pre-specified goals for lifestyle change, and were reassessed a year later.

“The issue of cardiovascular risk assessment is now central to primary prevention,” concluded Wood.

“For general practitioners the first challenge is to identify the high-risk people in their practice and then the second challenge is to manage that risk. That’s where the EUROACTION program provides an evidence base and a practical approach.”

Singapore doctors urged to raise awareness of prostate disease

Medical Tribune August 2008 SFI
David Brill

Many Singaporean men are suffering prostate problems in silence, according to a recent survey.

While 75 percent of those questioned had experienced symptoms of benign prostatic hyperplasia (BPH), just 56 percent had visited their doctor.

The majority of those who had symptoms had been suffering for at least 6 months, and half of those who did seek medical attention reported that urinary issues had begun to get in the way of their lives.

Nearly all of the men in the study felt that BPH was simply a natural part of growing old rather than a medical condition.

The president of the Singapore Urological Association (SUA) called for more to be done to raise public awareness of prostate disease.

“It is really a shame that here is a disease [BPH] that is eminently treatable, but many men are unaware that this is actually a disease and therefore do not seek treatment,” said Associate Professor Kesavan Esuvaranathan, who is also the clinical director of the National University Hospital Urology Centre.

“In the same way that elderly people will not go to the doctor and say ‘my hair is whitening’, they also don’t go to their doctor and say ‘I’m having difficulty with urination’, because all their buddies are having the same problems.”

GPs should ask their patients about prostate issues but be careful with their choice of approach, he said.

“The question they should not ask is ‘do you have a problem with urination?’ because invariably patients will say no.

“The questions they have to ask are: ‘Do you wake up at night to visit the bathroom? Do you have to wait a long time to finish? Are you bothered by these symptoms?’”

Once this type of dialogue is initiated and problems identified, doctors can go further and begin to provide treatment, Esuvaranathan said, adding that private healthcare doctors tend not to ask these questions so patients are less forthcoming with seeking advice.

Besides BPH, he noted that the incidence of prostate cancer has grown “exponentially” in Singapore and is now in the top ten leading causes of death from cancer.

The survey, which involved 480 Singaporean men, was conducted in July as part of Prostate Awareness Month – a national campaign by the SUA to educate the public about prostate disease and encourage people to seek early treatment.

Over the course of the month various hospitals offered screening to men aged 50 to 75 at a subsidized cost of $8. The campaign began with a free public forum at Kallang Community Centre, which was attended by 920 men.

The most commonly-reported concerns about BPH were physical discomfort caused by the inability to urinate properly, tiredness due to a lack of normal sleep, and the inconvenience and impact that the condition had on relationships and family life.

Treatment options for BPH include medications such as alpha blockers and 5-alpha reductase inhibitors, and surgery. For prostate cancer radiation therapy, hormone therapy, chemotherapy and surgery can be used, depending on the case.

Singapore joins UK on infectious disease research

Medical Tribune August 2008 SFI
David Brill

Singapore and the UK are to invest a total of $6m in infectious disease research as part of a collaborative project unveiled recently at Biopolis.

The Agency for Science, Technology and Research (A*STAR) and the UK’s Medical Research Council (MRC) are to contribute $3m each to the fund.

The money will be spent directly on joint research projects, which are expected to focus on the identification of disease biomarkers and the development of new vaccines and diagnostic tests.

“This joint collaborative research fund bears testimony to the success of the ‘UK-Singapore Partners in Science’ programme and builds on the excellent exchange and interactions between the scientists from both sides,” said Mr. Lim Chuan Poh, chairman of A*STAR.

“The collaboration will also lead to more opportunities for our A*STAR scholars to pursue research attachments and training respectively at MRC units in the UK, as well as develop new PhD projects between the supervisors in Singapore and their partner supervisors in UK universities,” he said.
The announcement was made ahead of a roundtable discussion to further develop ideas and agree on a course of action for tackling infectious diseases. Other attendees included Mr. Ian Pearson, the UK Minister of State for Science and Innovation, and Professor Sir Roy Anderson, a prominent expert on infectious diseases and the incoming Rector of Imperial College, London.

Pearson, who co-hosted the discussion with Lim, said: "This significant new collaborative fund brings the best of Singapore and UK science together to fight infectious diseases.

“I would like to see similar partnerships tackling problems in other scientific fields.”
Infectious diseases are estimated to account for 20 percent of all deaths worldwide, and are the leading cause of mortality in developing countries according to WHO data.

Chinese rice extract could be superior to statins for coronary prevention

Medical Tribune August 2008 SFIX
David Brill

A compound extracted from red yeast rice can significantly reduce the risk of coronary events among patients with a history of myocardial infarction (MI), a randomized trial involving 4,870 Chinese patients has demonstrated.

The magnitude of the effect surpasses that previously reported for statin monotherapy, according to the authors of the study which was published in The American Journal of Cardiology.

Major coronary events occurred among 10.4 percent of patients who took placebo and 5.7 percent of those who took the extract – correlating to a relative decrease of 45 percent and an absolute decrease of 4.7 percent.

The compound, known as Xuezhikang (XZK), was also associated with a 30 percent reduction in risk of cardiovascular death and a 33 percent reduction for total mortality. The average treatment duration was 4.5 years.

“This study shows very clearly that the results exceed that which you would find with any of the statin studies done with patients that have average cholesterol levels,” said Dr. David Capuzzi, one of the authors of the trial, which was conducted at 65 hospitals across China.

“I think it’s very promising. I would be surprised, quite frankly, if this turned out not to be an excellent product.”

He added that the closest comparable study is the Cholesterol and Recurrent Events (CARE) trial, which demonstrated that taking pravastatin led to a 24 percent reduction in risk and an absolute difference of 3 percent. [N Engl J Med 1996 Oct 3;335(14):1001-9]

XZK, which is produced by the Beijing WBL Peking University Biotech Co. Ltd., contains lovastatin, lovastatin hydroxyl acid and ergosterol, among other components. Patients who took 600 mg of XZK orally twice a day also showed significant decreases in triglyceride and LDL cholesterol levels and increases in HDL cholesterol levels compared to those who took placebo.

Dr. Paul Chiam, an associate consultant in the Department of Cardiology at the National Heart Centre Singapore, said that XZK has the potential to become a useful drug for patients who need lipid lowering treatment.

“XZK appears to be at least as effective and perhaps more effective than conventional statins reported in previous studies.

“However, the population in this study was different from studies of statins in the literature, and only a direct randomized head-to-head comparison between XZK and a well established statin, such as simvastatin, would resolve the question whether XZK is indeed more effective,” he said.

Chiam added that although XZK appears to be well tolerated, longer-term safety data are still required. At present a statin would still be first choice for the majority of patients, he said.

Capuzzi, who is based at the Lankenau Institute for Medical Research in Pennsylvania, US, stressed that XZK is extracted from rice grown under controlled laboratory settings and that the results cannot necessarily be extrapolated to commercially-available red yeast rice which may contain unknown compounds.

Improved lifestyle may cut sudden cardiac death risk

Medical Tribune August 2008 SFIX
David Brill

Primary care doctors can do more to lower the risk of sudden cardiac death (SCD) among their patients, according to a Singapore cardiologist.

Eighty percent of cases of SCD are thought to be caused by underlying coronary artery disease (CAD).

Many of these deaths could therefore be avoided by better tackling CAD, said Dr. Seow Swee Chong during the recent 39th National Medical Convention of the Singapore Medical Association.

“I think that awareness [of SCD] is not that high yet – particularly in the primary care setting,” he said.

“We are hoping that at the primary healthcare level we can have very good control of risk factors and lifestyle modification to prevent heart disease, and for these doctors to identify those who are at higher risk and refer for further assessment by a specialist so that appropriate therapy can be given.”

Tackling CAD begins with prevention, said Seow, a consultant at the Heart Institute, National University Hospital.

“The risk factors are smoking, high blood pressure, diabetes, high cholesterol, sedentary lifestyle and obesity. If you have these risk factors they should be treated and controlled adequately.”

He added that patients should be screened at a certain age to identify silent risk factors. For men this should be done at around 40 and for women around 50, he said.

Early detection of CAD is also important in reducing the risk of SCD. Treadmill exercise testing and cardiac nuclear perfusion scans can be used to demonstrate ischemia, while CT, MRI and coronary angiography can be employed to visualize the coronary arteries.

Once CAD is identified “we have to be aggressive and consistent in our treatment,” said Seow.

“We need then to bring the cholesterol and blood pressure down to adequate levels to prevent progression of disease, and give other medications to reduce the chance of heart attack, like beta blockers and aspirin.”

He referred to studies showing that statins can reduce overall mortality in patients who have heart failure, while the aldosterone antagonist eplerenone reduces morbidity and mortality in post-myocardial infarction patients with left ventricular dysfunction. [Am Heart J 2007 Apr;153(4):573-8; N Engl J Med 2003 Apr 3;348(14):1309-21]

Implantable cardioverter defibrillators (ICDs) have also been shown to reduce the risk of SCD in selected patients. For primary prevention, the decision to use an ICD should be made on the basis of certain criteria such as the patient’s left ventricular ejection fraction and the presence of tachycardias on electrophysiological testing, Seow said.

Patients who have already survived a cardiac arrest are at very high risk of recurrence, however, and ICD use among this population should be considered as standard for secondary prevention of SCD, he said.

More local data needed for athlete screening programs

Medical Tribune August 2008 SFV
David Brill

The introduction of a national screening program in Italy has helped to substantially reduce the incidence of sudden cardiac death (SCD) among young athletes.

However more regional data is needed before introducing similar programs in Singapore, a cardiologist has advised.

Speaking at the National Medical Convention of the Singapore Medical Association in July, Dr. Ong Hean Yee said that the results from Italy were “very, very impressive,” but noted that the causes of SCD in athletes vary around the world.

While hypertrophic cardiomyopathy is highly prevalent in the US, for example, arrhythmogenic right ventricular dysplasia and congenital heart disease seem to be responsible for more cases of SCD in Italy.

“In South East Asia we do not know. We do not have the data on the prevalence of cardiac abnormalities,” said Ong, a consultant cardiologist at Alexandra Hospital who was part of the medical committee for last year’s Standard Chartered Singapore Marathon.

“What works for the Italians might not work for Singapore. The demographics are quite different and we don’t want to be spending time and money doing something which doesn’t work.”

Italy introduced nationwide preparticipation screening in 1982. Research published in 2006 showed that the annual incidence of SCD in athletes dropped by 89 percent between 1979 and 2004 – from 3.6 to 0.4 deaths per 100,000 person-years. [JAMA 296(13):1593-601]

A total of 55 SCDs occurred among screened athletes during this period, compared to 265 deaths among those who were not screened.

Ong believes that awareness of the benefits of screening needs to be raised among the medical community.

“I think doctors are afraid because of all the negative publicity. But the guidelines are quite simple to follow, and if non-specialists do what the European Society of Cardiology [ESC] recommends they cannot go too far wrong,” he said.

Screening guidelines are also available from the American Heart Association (AHA), including a simple 12-step process covering personal history, family history and physical examination. [Circulation 2007 Mar 27;115(12):1643-455]

The ESC guidelines are similar but include performing a 12-lead electrocardiogram as standard. [Eur Heart J 2005 Mar;26(5):516-24]

At Alexandra Hospital, Ong said, screening follows the AHA’s 12 steps but includes electrocardiography, lipid and glucose testing, and a urine dipstick.

People who are at high cardiovascular risk, have a family history of heart disease, are aged over 40, are novices, or are doing very high-intensity sports should presently be screened, he said.

Ong added that it is currently hard to know where to draw the line between people who should obviously be screened and those for whom it is unnecessary. The issue of automated external defibrillators – at which events they are required, how many, and where to place them – also remains undefined.

He also described the reliance on further testing to identify heart problems as a “very controversial” area, noting that tests such as MRI, electrocardiography and the exercise treadmill test can all yield false negatives.

“There are a lot of unanswered questions,” he concluded.

Nonadherence to epilepsy medication triples risk of death

Medical Tribune August 2008 SFVII
David Brill

Patients who do not take their epilepsy medications have a threefold higher risk of death, a recent study has shown.

Researchers from the US studied health insurance claims data from 33,658 people over nine years and divided them into quarterly periods defined as either adherent or nonadherent to medication.

They found that the hazard ratio for mortality during nonadherent quarters was 3.32 (95 percent CI 3.11 – 3.54). These periods were also associated with significantly more emergency department visits, hospitalizations and fractures.

“These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy,” the researchers wrote in Neurology.

They also report that nonadherence was more common among males, patients aged over 65, and African Americans.

Lead author Professor Edward Faught, who is director of the University of Alabama Epilepsy Center, said that doctors should educate patients about the need to take their medications but should be careful not to frighten them excessively.

“It might be counterproductive to be blunt and say ‘if you don’t take your medications you may die,’ but I think it certainly is appropriate for physicians to tell patients that there’s good evidence that serious injuries and hospitalizations, which could result in permanent or fatal results, are known to occur if medications are not taken regularly,” he said.

Faught added that primary care physicians are well placed to discuss medication adherence with their patients, as they typically see them more often than neurologists and may have a better personal rapport.

“It’s important once one initiates a dialogue with the patients about adherence to go further and find out what the problems are,” he said.

“Do they think that it’s not necessary – that they can take it just occasionally and they’ll be fine? Is the medication causing side effects? Is it an economic issue? Or is it simply a problem with the daily schedule?”

The research was based on Medicaid data from Florida, Iowa and New Jersey, compiled between January 1997 and June 2006.

One limitation to the study is that the database does not provide information on the specific causes of death and it cannot be proven that epilepsy was responsible, Faught said.

Dr. Andrew Pan, a consultant neurologist and epileptologist at Mount Elizabeth Medical Centre, said that the same principle applies to the increased incidences of hospitalization and fractures, which were not necessarily caused by epilepsy.

He added that the findings may not be applicable to the general population as patients on Medicaid are likely to be from a lower socioeconomic group.

“Patient compliance to antiepileptic drugs should be routinely checked, especially if seizure control does not appear satisfactory,” Pan concluded.

“It is important that the patient feels that the doctor is working with them to help them with their quest for seizure control.”

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.

Topiramate effective for treating alcohol dependence

Medical Tribune August 2008 SFIX
David Brill

A randomized trial has shown that topiramate can improve the physical and mental wellbeing of alcoholics as well as reducing their drinking behaviour.

Patients who took the drug over a 14-week period displayed a greater overall clinical improvement and a reduction in obsessional thoughts and compulsions about using alcohol compared to those who took placebo.

Topiramate was also associated with significant improvements in liver function and reductions in plasma cholesterol, body mass index and blood pressure.

“The research shows quite clearly now that medications add to the beneficial effects of psychotherapy or psychosocial interventions,” said the study’s lead author Professor Bankole Johnson, who is chairman of the department of psychiatric medicine at the University of Virginia, US.

The use of topiramate as a treatment for alcohol dependency is currently off-label in the US and Johnson does not specifically advocate the drug over any other.

“If anyone with alcohol dependence presents to a family practitioner or a general practitioner then it’s important that medication be prescribed, whatever the medication. Otherwise they’re not getting the best effect of treatment,” he said.

He added, however, that topiramate does appear to be more powerful and efficacious than other options such as naltrexone or acamprosate.

The double-blind trial, published in The Archives of Internal Medicine, involved 317 alcohol-dependent patients aged from 18 to 65.

Patients in the topiramate group also reported improvements in some aspects of quality of life such as leisure-time activities and household duties, and displayed a trend towards reduced sleep disturbances. However adverse events – including pins and needles, headache, fatigue, nausea and anorexia – were more common among these patients than those who took placebo.

Topiramate is thought to reduce the rewarding effects of alcohol consumption by working on the corticomesolimbic system – inhibiting glutamate pathways while facilitating γ-aminobutyric acid pathways.

Previous studies had shown that the drug reduced alcohol consumption and promoted abstinence, but had not addressed the physical and psychosocial aspects of treatment.

“To have a medicine that can not only reduce the alcohol drinking but can also help improve these other problems is very important,” said Johnson, adding that topiramate can be prescribed for patients who are still drinking and not just those who are abstinent.

“And I think there’s an important public health message,” he added. “We need to find ways to treat this disease that are effective and easy to deliver because it’s number five on the World Health Organization’s global impact of disease list, and we really need treatments that all doctors can deliver and not just specialists.

“In the US we’re now getting a slight increase in the number of doctors prescribing medicine for alcohol dependence and I’m hoping that that trend will continue,” he said.

New bird flu vaccine promises broad immunity and rapid manufacture

Medical Tribune August 2008 SFXII
David Brill

A new vaccine against the avian influenza H5N1 virus has been shown to be well tolerated and induce high levels of immunogenicity against a variety of strains.

The vaccine is derived from continuous cell culture and could be produced up to 3 months quicker than by using traditional methods, the manufacturers suggest.

Mr. Peter Carrasco, Policy Advisor on Vaccine Security for WHO, said that the vaccine could be useful for protecting against viruses that are currently circulating in infected birds, but added that more research is needed with larger study groups to reconfirm the trial’s findings.

The vaccine was tested in a randomized phase I and II trial involving 275 subjects who received two doses 21 days apart. The results were published in The New England Journal of Medicine.

A dosage of 7.5 mcg without adjuvant induced a neutralizing-antibody response in 76.2 percent of subjects – equivalent to a seroconversion rate of 69 percent. Immunogenicity was seen not only against the clade 1 strain used to produce the vaccine (A/Vietnam/1203/2004), but also extended to the clade 2 and 3 strains.

Conventional H5N1 vaccines are produced using embryonated chicken eggs – a technique that requires the use of an attenuated version of the virus. Cell culture, however, can be used to generate a vaccine from the wild type, thereby eliminating the delay while a modified virus is produced.

“The lag time between receipt of a new virus and delivery of a new vaccine is only something like 12 weeks using our technology, which is about 3 months quicker than can be done with the egg technology,” said Dr. Noel Barrett from the Department of Global Research and Development at Baxter BioScience, who developed the vaccine.

“We’re faster, we’re more flexible, and the process is much more robust in that we’re not dependent on the supply of hen’s eggs, which is an uncertain factor in the event of a pandemic caused by an avian virus.”

Baxter have submitted a licensing application for the vaccine to the European Medicines Agency (EMEA), and expect a decision early next year.

The company has reached agreements with some countries to provide the vaccine in the event of a pandemic and already has the manufacturing capacity to deliver in a relatively short time, Barrett said. The decision whether to implement pre-pandemic vaccination remains a matter of government policy, he added.

One potential drawback to the new vaccine is the need for enhanced biosafety facilities which can handle the virulent wild type virus.

“There are very few facillities which are biosafety level 3, and these are expensive to maintain,” said Associate Professor Paul Ananth Tambyah, head of the Division of Infectious Diseases at the National University Hospital in Singapore, who was also one of the authors of the study.

“Without them it is not safe to manufacture this vaccine,” he said, adding that these manufacturing hurdles would need to be overcome before the vaccine could be used routinely.

NHG boosts budget for healthcare training awards

Medical Tribune August 2008 SFXV
David Brill

An extra $2 million is being invested in further training for health professionals, the National Healthcare Group (NHG) announced recently.


This year’s Health Manpower Development Plan (HMDP) Fellowship Awards are to total around $6 million – an increase from last year’s figure of $4.1 million.

The awards, which are also supported by funding from the Ministry of Health (MOH), enable healthcare workers to undergo specialist training attachments at institutions in Singapore and overseas.

A total of 138 NHG staff – 50 doctors, 48 nurses, 35 allied health professionals and 5 administrators – were named as awardees by Mr. Michael Lim, Chairman of NHG.

“The HMDP allows our healthcare professionals to keep abreast with the best and most advanced in the world,” said Lim in a speech at the Institute of Mental Health (IMH).

“Medicine is a talent-intensive business so we must continue to invest in our people … we will use the HMDP awards to fill gaps in our healthcare system to meet the cluster’s long-term strategic plans and national priorities.”

Three new categories of award have been created, including the MOH HMDP Fellowship in Mental Health, which provides full sponsorship for further study in occupational therapy, clinical psychology and other areas within the field.

Ms Huang Wanping, one of the recipients, is presently a psychologist at the IMH having previously worked with the Singapore Police Force. The award will enable her to specialize as a clinical neuropsychologist by completing a 2-year masters at the University of Melbourne, Australia.

The other new categories are the MOH HMDP Award for Strategic Nursing Development, and the HMDP (Team Based) award, which was given to teams from National University Hospital, Tan Tock Seng Hospital and the National Skin Centre.

The HMDP was created in the 1980s by the MOH, but administration has since been devolved to NHG and SingHealth. The programme is responsible for inviting overseas expert to lead training programmes in Singapore, as well as sponsoring the nation’s healthcare workers to undertake further training abroad.

Mediterranean diet reduces diabetes risk

Medical Tribune August 2008 SFXV
David Brill

Following a Mediterranean diet – known to lower cardiovascular risk – can also reduce the chance of developing diabetes, Spanish researchers have shown.

The study, which was published in the British Medical Journal, followed 13,380 university graduates over a median period of 4.4 years and used questionnaires to rank their adherence to the diet on a scale of one to nine.

“Those who were highly adherent to this traditional dietary pattern exhibited a very low rate [of diabetes] and an impressive magnitude in the relative risk reduction of 83 percent,” said lead researcher Miguel Martinez-Gonzalez, Professor of epidemiology at the University of Navarra.

Interestingly, he added, people who adhered most closely to the diet were typically older with a higher prevalence of hypertension, smoking history and other risk factors for diabetes. The incidence among this group would therefore have been expected to be high.

“This may mean that the Mediterranean diet is highly protective against diabetes,” he said, but added that only 33 new cases were observed – a small number relative to the size of the study.

“This is fortunate for our participants indeed but this is a major limitation. We need further evidence from larger cohorts and trials,” he said.

The traditional Mediterranean diet comprises high amounts of olive oil, fruit, vegetables, nuts and fish, and relatively low amounts of meat and dairy products. The health benefits of the diet have been shown in various studies, including a randomized trial which demonstrated a beneficial effect on cardiovascular risk factors. [Ann Intern Med 2006 Jul 4;145(1):1-11]

Dr. Warren Lee, former Chairman of the Diabetic Society of Singapore, said that the study was interesting and comprised good quality data.

“I would certainly say this reinforces the old chestnut that one should take more fruit and vegetables and emphasize less on the meat,” he said.

It remains unclear at what point of adherence to the diet the benefits begin to accrue, added Lee, who is a pediatric endocrinologist in private practice and a senior consultant at KK Women’s and Children’s Hospital.

"This study was not able to show a threshold effect because it was designed to show that there was an effect in a relatively homogenous population of people who ate either more than the mean or less than the mean of certain foods.

“However it was heartening that a two point increase in a nine point score was able to reduce the incidence rate ratio – a measure of relative risk – by 35 percent, and that even those in the moderate adherence group had a significant benefit. This suggests that people trying to adhere to a healthy diet will be better off than those who do not even try,” he said.

Lee noted that the diet in Spain is rather different to that in Singapore, where food is frequently cooked using palm oil or pork lard rather than olive oil.

“Perhaps the next step is to see how we can incorporate elements of this diet into our food choices,” he concluded.

Doctors cure advanced skin cancer using T-cell clones

Medical Tribune August 2008 P12
David Brill

Researchers in the US have successfully treated a man’s skin cancer using laboratory-cloned T cells.

The team from the Fred Hutchinson Cancer Research Center in Seattle isolated and expanded autologous CD4+ T cell clones specific to the tumor antigen NY-ESO-1, and infused some five billion copies into a 52-year-old patient with refractory metastatic melanoma.

Computed tomography and positron emission tomography scans performed two months later showed that the patient’s tumor had completely regressed, and he remained disease free at 2 year follow-up.

His cancer had previously not responded to treatment with interferon alpha, interleukin 2 or local excision, and had spread to the groin, lung and left ilium.

Dr. Cassian Yee, who led the study, said that although the response was good in this case, more studies would be needed to confirm the efficacy of the procedure.

“This was just a small step, hopefully in the right direction,” he said, adding that the approach was only tested in patients with melanoma and the results should not be considered to apply to all cancers at this point.

The cloned CD4+ cells persisted in the patient’s blood for over 3 months without cytokine treatment – in contrast to CD8+ T cells which have been found to survive for less than 20 days without exogenous cytokines.

“Cell therapy represents a new vista in the treatment of cancer,” said Dr. Toh Han Chong, a senior consultant in the department of medical oncology at the National Cancer Centre Singapore (NCCS).

“It’s real – the fact that one patient had a long remission is great. But of course it doesn’t mean that if you treat a hundred patients all hundred will get a complete remission.”

A similar approach for patients with nasopharyngeal cancer is shortly to enter a phase II clinical trial at NCCS according to Toh, who is also an associate investigator in the laboratory of cell therapy and cancer vaccine. The trial is expected to last 3 years and will comprise 35 patients, each receiving 6 separate infusions of cloned T cells.

Writing in The New England Journal of Medicine, Yee and colleagues reported that T cells against other tumor antigens – MART-1 and MAGE-3 – were also found in the patient’s blood after the procedure, having been undetectable beforehand. This apparent extension of the immune response could explain why the tumor regressed completely despite the fact that only 50 – 75 percent of its cells expressed NY-ESO-1, the researchers said.

Nine patients were treated in all. Some others exhibited stabilization of their disease but it remains unclear why only one displayed complete regression, Yee said.

He added that T cell therapy could become more common in future, but at present the process requires very specialized equipment and training, and around 4 months is needed to grow the clones.

“Hopefully we can streamline that process a bit but it’ll never be like a drug that you can just take off the shelf,” he concluded.

Naltrexone reduces gambling urges and behavior

Medical Tribune August 2008 P13
David Brill

The opiate antagonist naltrexone could be an effective treatment for pathological gambling (PG), according to research from the University of Minnesota.

Participants who took the drug during an 18-week randomized trial had significant reductions in gambling urges and behaviour compared to those who took placebo, and displayed improvements in overall gambling severity and psychosocial functioning.

Naltrexone, which is typically used for alcohol and opiate dependence, was well tolerated at doses of 50, 100 and 150 mg/day.

Dr. Jon Grant, lead researcher of the study, said that the findings were very encouraging.

“We were excited because although we found that there was no difference in terms of response to different doses, the medication was still significantly better than placebo,” he said.

The study supports the use of medications as a tool to treat PG, according to Grant, who hopes that naltrexone will be offered routinely for future patients. He added however that there are many different options for treating PG, and that a combination of multiple interventions is likely to be most effective.

Ms. Elda Mei-lo Chan – supervisor at the Tung Wah Group of Hospitals Even Centre in Hong Kong which treats some 700 problem gamblers each year – stressed the importance of performing a holistic assessment before deciding on the appropriate treatment for each patient.

“Gambling is a very complex problem so you really have to look at the underlying causes of the behaviour,” she said, noting that medications can be effective for those whose urges are triggered by biological or neurological factors, whereas others may gamble to boost their self esteem or as a form of protest against problems in their life.

Chan added that patients receiving drug therapy should also receive some form of psychotherapy to help them fully understand the role of the medications.

“We’ve seen too many cases who come here and expect a couple of pills to solve everything. That’s not a realistic way of dealing with the problem – they really have to have the ability to improve relationships with their families and change their lifestyle so that they can still continue their work and their normal day-to-day life,” she said.

The trial involved 77 pathological gamblers, as defined by the Diagnostic and Statistical Manual of Mental Disorders. The positive treatment effect of naltrexone reached significance after 6 weeks. [J Clin Psychiatry 2008 Epub ahead of print]

Prior to enrollment, participants gambled for an average of 13.1 hours and lost US$535.54 per week. Having money was reported as the most common trigger for gambling urges, followed by stress, loneliness and advertisements.

Gambling behaviour and urges were assessed using a range of diagnostic tools, including the Yale-Brown Obsessive Compulsive Scale. Patients who improved during the trial said that they felt greater control over their actions and less of an impulse to act immediately on their urges, Grant said.

The study replicates and extends the results of previous studies into naltrexone for PG, carried out by the same group.

New partnership launched to accelerate TB drug research

Medical Tribune August 2008 P13
David Brill

A new collaboration was announced in Singapore last month that aims to facilitate the development of new drugs for tuberculosis (TB).

The 5-year agreement will allow information and ideas to be shared between the Novartis Institute for Tropical Diseases (NITD) and the Global Alliance for TB Drug Development (GATB), with a particular view to discovering drugs that work on resistant strains of TB.

“TB as an area is in desperate need of new drugs,” said Professor Paul Herrling, chairman of the board of the NITD.

“The essence of this is that we open our entire research protocol to the GATB. If we have a drug that looks promising for full development in TB, based on this agreement we can give them the exclusive license. It’s a very good thing.”

Shortening the duration of treatment is one of the major aims of the research, Herrling said. Current anti-TB drugs typically need to be taken for 6 to 9 months but resistance can develop when patients do not complete the course.

The project also seeks to find new drugs that are cheap to produce, easy to use, and do not interfere with HIV combination therapy.

The GATB – a not-for profit group which works with both private and public laboratories – is experienced in the later stages of drug development and in delivering new products to patients, Herrling said, whereas the NITD focuses on the early stages from the basic science through to proof of concept in humans.

“They really need a constant inflow of new compounds, and we are one of the suppliers. So it’s win-win in the sense that we produce what they want, and then they take our compounds and move them on beyond the stage that we would,” said Herrling, who is also a former vice president of the board at GATB.

TB was responsible for 1.7 million deaths in 2006, according to data from the World Health Organization. Almost half a million new cases each year are multidrug-resistant, with the highest-ever rates reported in 2008.

“One of the important changeovers [in drug discovery] is between the research part and what comes after,” said Herrling, adding that the new collaboration should speed up this part of the process.

“If you don’t do it well you lose a year or two or maybe even more at this interface, and that’s a bad idea because while you wait people are dying at the other end,” he concluded.

Chronic kidney disease: Asia’s ‘silent epidemic’

Medical Tribune August 2008 P14
David Brill


Reducing chronic kidney disease (CKD) should become a public-health priority, according to the authors of a large prospective study which found the national prevalence of the condition in Taiwan to be 11.9 percent.

This figure puts the condition on a par with smoking and obesity as a leading cause of death, the researchers wrote in The Lancet.

Awareness among the study population was low – just 3.5 percent of people knew that they had CKD.

The study, which followed 462,293 people over 13 years, also found that CKD is much more prevalent among lower socioeconomic groups, and that the regular use of Chinese herbal medicines carries a 20% increased risk for developing the condition.

“I think this is a silent epidemic,” said the study’s lead author Dr. Chi Pang Wen, from the National Health Research Institutes in Taiwan.

“It’s growing globally, and particularly Asians need to be even more concerned because of our fondness of taking medicine, including Chinese herbal medicine. The seriousness of this has not been well appreciated because people are only looking at the tip of the iceberg, which is the people on dialysis,” he said.

People with CKD were twice as likely to die from cardiovascular causes and 1.83 times as likely to die from any cause, the study found. Almost 40 percent of those who died were aged less than 65. [Lancet 2008 Jun 28;371(9631):2173-82]

The study highlights the importance of modifying risk factors such as hypertension, diabetes and smoking said Wen, who noted that the kidneys seem to be the earliest warning signal for vascular problems that may lead to cardiovascular death.

He called on the whole medical establishment to get involved with tackling the burden of CKD, beginning with the laboratories.

“When they report creatinine they need to have a formula to convert it into glomerular filtration rate (GFR). Without that conversion most Asian doctors are looking at creatinine which does not have as a high a level of sensitivity as GFR and cannot classify people into the 5 stages of CKD,” he said.

Wen added that the public should be encouraged to ask their doctor about their GFR value and whether or not they have proteinuria, which is an important warning sign for CKD.

Dr. Chan Choong Meng, Head and Senior Consultant in the Department of Renal Medicine at Singapore General Hospital, said: “This study shows that patients of a lower socioeconomic status are more susceptible to developing CKD. Unfortunately, they are likely to be unaware of the disease until a later stage.

“Early detection by screening and treatment for diabetes and hypertension will help reduce the burden of CKD, and early treatment will help in preventing and retarding the progression of the disease,” he said.

Chan added that the rates of CKD observed in the study are comparable to those previously documented for the US and Norway.

Diagnosing and managing osteoporosis in primary care

Medical Tribune August 2008 P15-16

Osteoporosis affects around a third of women aged 60 – 70 and two thirds of those aged 80 and above. The condition also affects men – approximately one in five of whom will suffer an osteoporosis-related fracture above the age of 50. Osteoporosis carries a significant burden in terms of hospitalization for fractures, and patients will typically experience increased morbidity, disability, and a reduction in independence.

Diagnosis

Osteoporosis is a silent epidemic, and overt signs are usually absent until a patient presents with a fracture. This is likely to be a fragility fracture caused by relatively low trauma – a sign that the bones have become weakened. Compression fractures of the vertebrae are a common presentation, while other types include Colles’ fractures of the wrist and hip fractures, both of which typically result from a fall.

There are several risk factors for osteoporosis that general practitioners (GPs) should be aware of, such as increasing age, frailty, a personal history of fractures and a family history of fractures (particularly on the maternal side). Loss of height is also common among patients, and suggests that the vertebrae are collapsing. Back pain may also be present – often signifying that the patient has an undiagnosed compression fracture.

It should also be noted that osteoporosis in men tends to have a later age of onset than in women. Consequently mortality from fractures is twice as high for men, so it is important that GPs retain a high suspicion for osteoporosis among their elderly male patients.

GPs can also encourage their elderly patients to use the Osteoporosis Self-Assessment Tool for Asians, which is applicable for post-menopausal women of Asian descent. This can help to identify patients at high risk, who can then visit their doctor for screening and further assessment.

The gold standard for diagnosis of osteoporosis is a bone mineral density (BMD) scan using dual energy x-ray absorptiometry, with osteoporosis defined as a T-score of minus 2.5 or lower. In the absence of any other cause, a fragility fracture can also be considered as a diagnosis for osteoporosis. Patients should also receive the relevant x-rays to fully document their fractures. It can be challenging for GPs to pinpoint osteoporosis in patients who have not experienced a fracture, as some patients might find the cost of the tests prohibitive. Access to BMD scanners can sometimes be problematic

Practice Guidelines

The Ministry of Health (MOH) in Singapore is currently revising its guidelines for osteoporosis, which were last published in 2002. The new version is expected to be available later this year. The Academy of Medicine of Malaysia also has its own guidelines for osteoporosis, the second edition of which was released in 2002.

Various guidelines and recommendations are also available from the International Osteoporosis Foundation (IOF) website, including IOF-endorsed guidelines published in 2008 by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This comprehensive 30-page document covers the diagnosis and management of the condition in postmenopausal women.

Recommendations and other helpful documents for the secondary prevention of osteoporosis are available from the National Institute for Health and Clinical Excellence (NICE), UK.

Treatment

There are many factors to consider when treating osteoporosis, and it is important to decide carefully on an appropriate strategy for each patient before proceeding with treatment.
Drug treatments are available but the cumulative costs can be formidable. The first decision physicians should take after making a definite diagnosis of osteoporosis, therefore, is whether or not to treat the patient. This decision should be based on the patient’s 10-year fracture risk, which can be calculated using IOF guidelines. A 65-year old at low fracture risk, for example, might not warrant the same treatment approach as a high-risk 85-year-old. In some cases it may be best to postpone treatment following diagnosis, monitor the patient closely and review the decision at a later stage.

Before initiating drug therapy it is important to obtain a BMD scan. This will provide a baseline value for comparisons, so that the long-term efficacy of therapy can be monitored.

Bisphosphonates, such as alendronate and risedronate, are the first-line therapy for patients who do merit drug treatment. Doctors should make their patients aware that these drugs must be taken according to certain instructions. Tablets should be taken on an empty stomach first thing in the morning, and the patient should refrain from eating for an hour afterwards or consuming any caffeine-containing drinks or milk products in this time. Failure to do so can render the tablet ineffective – which may be an explanation in cases where BMD is not improving. Elderly patients may also forget to take the drugs, or take them but forget that they have done so and lie down shortly after, which can cause painful esophagitis.

Other drug treatments include strontium ranelate, raloxifene and parathyroid hormone injections (such as teriparatide).. Annual injections of zoledronic acid, a form of bisphosphonate, have also been shown to reduce the risk of fractures and the data in support of this option are promising. The injection can be expensive, however, and some patients might prefer treatments that spread the cost out over the year.

GPs should prescribe calcium supplements for patients who are deficient, which can be a common problem in Asian countries where dairy consumption is low. The recommended intake at different ages can be found in the guidelines. Boosting calcium levels can also serve as a prevention strategy, and GPs should also encourage the use of supplements in non-osteoporotic elderly patients who are at high risk.

Lifestyle management is also a key aspect of treating osteoporosis in the primary care setting. Ill-health can lower general nutrition, leading to further reductions in calcium levels, so a healthy diet should be promoted for all cases. Osteoporotic patients should be advised not to drink or smoke, and should also be encouraged to perform weight-bearing exercises at least three times per week for 50 – 60 minutes at a time in order to improve strength and co-ordination and reduce bone loss.

Disease management tools

Elderly patients living in the community have a roughly 30 percent chance of falling in a year, and fall prevention strategies are an important tool for reducing the risk of fractures among those with osteoporosis.

Falls typically result from a combination of several underlying causes. Risk factors such as poor gait, eyesight, and neurological comorbidities should be addressed where possible, which may require collaboration between different medical disciplines. Psychologically-altering medications such as antipsychotics and sleeping tablets can also increase the risk of falls, and may need to be adjusted accordingly.

Physicians may also need to consult with occupational therapists and physiotherapists, and in some cases might choose to encourage patients to make modifications to their home environment. Suggestions can include improving lighting, anchoring carpets and rugs, securing loose wires and applying non-slip mats to stairs and bathroom floors.

Further information on osteoporosis and home care solutions can usually be obtained from specialist centers and clinics, and GPs should refer their patients onwards for further advice and treatment where appropriate.

Conclusion

Managing osteoporosis in the primary care setting begins with an accurate diagnosis. GPs should remain vigilant for patients who have a history of fragility fractures or falls, and remember that men are also at risk for the condition. Once osteoporosis is identified, doctors should choose carefully from the range of available treatment options and select the strategy that is best suited to the patient.