June 2013

www.medicaltribune.com

IOF campaign aims to reduce fractures worldwide

Premature ejaculation negatively impacts relationships

EXPERT OPINION

Managing dengue ever in primary care

IN PRACTICE

CONFERENCE

AFTER HOURS

All Things Golden – New Zealand’s Golden Bay

Chronic pain a hidden disease, warrants attention

2 June 2013

Chronic pain a hidden disease, warrants attention

Rajesh Kumar

Chronic pain is not merely a symptom, but a hidden disease in itself that de-serves to be a health care priority in

every country, according to an expert.“The evidence is now overwhelming that

chronic pain can be a chronic disease,” said Professor Michael Cousins, professor of an-esthesia at the Northern Clinical School and Kolling Institute of Medical Research at the University of Sydney, Sydney, Australia, speaking during the recent 5th Association of South East Asian Pain Societies (ASEAPS) conference held in Singapore.

“You only have to think about a person with a very severe osteoarthritis of the hip joint who has hip replacement surgery. The surgery resolves the arthritis and the prob-lem goes away. But that doesn’t always hap-pen. About 10 to 15 percent of the patients do not have that outcome. Clearly they had two diseases: osteoarthritis of the hip and chronic disease of chronic pain.”

Pain management remains inadequate in most parts of the world, with poor access to the treatment for chronic, acute and even cancer pain, said Cousins. While recogniz-ing chronic pain as a chronic disease is im-portant, he said the US Institute of Medi-cine in a groundbreaking 2011 report titled Relieving Pain in America did just that by providing a blueprint for transforming pre-vention, care, education and research into chronic pain.

Ironically, the acknowledgment of chronic pain as a chronic disease seems to have be-come one of the biggest barriers in itself to moving ahead on the issue.

“Where on earth is the management of chronic pain going to be sited in the health-care system, if not in chronic disease side?” Cousins asked, while making a case for pain medicine as a specialty in its own right.

Recalling the contribution of Professor John Bonica, considered the godfather of pain management, Cousins said Bonica was way ahead of his time when, in 1946, he began put-ting together a multi-disciplinary approach to the diagnosis and treatment of pain – an ap-proach that is sorely needed today.

“In 1960, he carried on this work at the University of Washington in Seattle [US] and recognized the importance of psycho-social factors contributing to chronic pain...that was [quite] futuristic for anesthesiologists,” said Cousins, adding that many more such pain champions are needed today.

Meanwhile, the WHO is currently pro-ducing evidence-based clinical guidelines on chronic pain and pediatric pain management. Several online training programs are also avail-able for physicians in Australia and elsewhere to upgrade their skills. But creating a core cur-riculum that defines the specialty of pain man-agement is crucial to bringing it the necessary credibility and recognition, said Cousins.

Chronic pain is a chronic disease which remains inadequately managed in most parts of the world.

3 June 2013

Working-memory training improves dyslexia

Imag

e cou

rtes

y of

Neu

ral R

egen

erat

ion

Res

earc

h.

Jackey Suen

Working-memory training can im-prove reading proficiency among Chinese children with develop-

mental dyslexia, a recent study has shown. [Neural Regen Res 2013;8:452-460]

“This study is the first to examine working-memory training in Chinese children with developmental dyslexia,” wrote the authors from the Huangzhong University of Sci-ence and Technology, and the Wuhan Men-tal Health Center in Wuhan, China. “To date, there is no evidence that training in any other aspect yields increased working-memory in dyslexic children. We hypothesized that working-memory abilities in those children would improve after training, and the im-provements would have a positive effect on their reading abilities.”

In the study, 30 dyslexic Chinese children (age 8-11 years) were recruited to receive working-memory training in visuospatial, ver-bal and central executive tasks. The children were divided equally into a treatment group (trained for 40 minutes a day for 5 weeks; task difficulty adjusted according to the comple-tion of training) and a control group (trained for 10 minutes a day for 5 weeks; difficulty level not interactively adjusted). Their per-formance in cognitive measures and reading ability was examined after training.

Results showed significantly improved per-formance in verbal working-memory, visuo-

spatial working-memory, central executive function, and literacy in the treatment group. However, no significant differences were found for any measures in the control group.

More importantly, visual rhyming and fluency were also significantly improved by training.

“Progress in working-memory measures was related to changes in reading skills. Our findings indicate that working-memory is a pivotal factor in reading development among children with developmental dys-lexia, and interventions to improve work-ing memory may help dyslexic children to become more proficient in reading,” the authors concluded.

While previous studies showed that dys-lexic children benefit from early interven-tion programs focusing on orthographic and phonological awareness training, these im-provements are more difficult to achieve for fluency than for accuracy.

4 June 2013 Forum

What place for medical tourism?There is often an emphasis placed on the benefits or value of ‘medical tourism’ within healthcare systems in various countries in the Asia region. During the recent Economist’s Healthcare in Asia conference held in Kuala Lumpur, Malaysia, Mr. Steven Thompson, chief executive officer of Johns Hopkins Medicine International and senior vice-president of Johns Hopkins Medicine, gave his views on what is a contentious issue. The following is an excerpt.

In the quest for value in a healthcare sys-tem I find ‘medical tourism’ to be a dis-traction. I don’t see examples of where it

actually improves value given to a system. I’m not arguing in any way the issues related to the business reasons for attracting medical travellers. I think there is a very clear business reason for medical tourism. There is a clear need with respect to the fact that people don’t have access to services that they need or wish for locally. However, having said that, I think that it is really incumbent on us all to have as a goal to make those kinds of services avail-able locally. [Some claim that] medical tour-ism is a means to add value to a healthcare system. However, I don’t see the connection.

One of the down-sides of medical tour-ism is that because there can be such an over-whelming incentive for local healthcare ser-vices to charge higher fees for a higher paying [foreign patient] population, this can in fact restrict access to the local population at local normative rates of service fees.

I take the point of others that the term medical tourism is in many respects a very ill defined term. As opposed to that of ‘medi-cal travel’, which has the connotation that it is something more acuity-driven versus completely discretionary. Therefore, I think there is a whole spectrum of ways to look at or define ‘medical tourism’. There is value which comes in many different ways by vir-tue of people travelling to access healthcare

services. However, the purpose of my com-ments, in addition to trying to be provocative, is that I would like to encourage people to be very clear about what the objective of medical tourism is. It is fine to have the objective of a business reason to do it because there is cer-tainly the benefit of cross-subsidization that comes from it. But the term is often not well defined and can mean something very differ-ent to different people involved in the health-care field.

Mr. Steven Thompson

5 June 2013 Forum

We are pleased to advise the change of our company name from UBM

Medica to MIMS, effective from 10th April 2013.

Across Asia-Pacific, MIMS has under-gone a major transformation in recent years through expansion of its services, of-fering solutions across multiple channels, strengthening and growing our network of healthcare professionals. Over 1 million members of the medical community now connect with MIMS through its suite of products across print media, online, insti-tution-based products and mobile applica-tions.

The name change to MIMS reflects our continuous expansion and innovations. With MIMS at the heart of our communica-tion and engagement hub, it will represent our entire business moving forward. This highlights our unique identity as a medical information and communication specialist dedicated to delivering total integrated so-lutions:• MIMS – Essential drug information pro-

vided in print, online (www.mims.com), tablet and smart-phone devices

• MIMS Healthcare Data – Integrated clinic decision support tools for health-care institutions

• MIMS Education – Professional publica-tions (Medical Tribune, Oncology Tribune, JPOG and Pharmacy Today) bringing the latest news from around the region and internationally

• MIMS MedComms – Providing our ex-pertise in medical communications and tailored solutions to meet your market-ing needs across event, print and digital media

• MIMS Events – Congress and event de-velopment and management services

• MIMS Consumer – Consumer health publications and resources such as HealthGuide, HealthToday and MOMSTo-dayWith this integration of our resources

and channels, we look forward to our continued partnership and thank you for your support.

With best regards, Ben Yeo CEO

Announcement: New Company Name – MIMS

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com

In this Series, find out about what these leading medical experts have to say about the latest updates in the management of asthma and COPD.

Professor Peter Barnesdiscusses advances in COPD management

SCAN TO WATCH VIDEO

Brought to you by MIMS

MIMS Video Series features 5-minute interviews with leading experts.

Professor Andrew McIvortalks about patient compliance in asthma treatment

Got a spare 5 minutes? Go to www.mims.asia/video_series

Management of asthma and COPD

MIMS Video SeriesBy DoctorS, For DoctorS

7 June 2013 Conference CoverageEuropean Congress on Osteoporosis and Osteoarthritis 2013, April 17-20, Rome, Italy

Elvira Manzano

Long-term treatment with the anti-os-teoporotic agent strontium ranelate (Protos®, Servier) delayed disease pro-

gression and improved symptoms in patients with knee osteoarthritis (OA), according to the findings of a large phase III trial.

In the multinational SEKOIA* trial, patients treated with strontium ranelate 1 or 2 g daily for 3 years had smaller loss of cartilage or joint space widths (JSWs) compared with placebo re-cipients (-0.23 and -0.27 mm, respectively, ver-sus -0.37 mm). Additionally, there were greater reductions in total WOMAC** score (a mea-sure of function, pain and stiffness) and knee pain (p=0.045 and p=0.065, respectively) with strontium ranelate 2 g/day. [Ann Rheum Dis 2013;72:179-86]

“The finding was significant as this structural effect is translated clinically into a lower number of patients with radiological progression over thresholds predictive of OA-related surgery,” said study author Professor Cyrus Cooper from the Epidemiology Unit, University of South-ampton, Southampton, UK. “A higher dose of strontium ranelate was, however, required for significant amelioration of symptoms.”

This suggests that the 2 g/day dose would be the most appropriate for clinical practice, added Cooper.

SEKOIA included 1,683 patients aged ≥50 years with knee OA of 7 years, randomized to strontium ranelate 1 or 2 g/day or placebo.

Strontinum ranelate is potentially beneficial in patients with knee OA in particular.

Strontium ranelate stems OA progression, symptoms

Baseline JSW was 2.5 to 5 mm. More than two-thirds were women. Primary endpoint was change in JSW over 3 years. Secondary end-points were radiological progression (joint space narrowing [JSN] >0.5 mm), knee pain and total WOMAC score. A lower score rep-resents less pain, less stiffness, or better physi-cal function.

The change in JSW from baseline was sig-nificantly greater with strontium ranelate com-pared with placebo at 1, 2 and 3 years. Patients on strontium ranelate also had lower subscores

8 June 2013 Conference Coverageon pain and physical function (p=0.028 and p=0.099, respectively).

The rate of venous thromboembolic events was similar (<1 percent) in all groups. Slight in-creases in creatinine phosphokinase were noted in the treatment groups, but these were mild, transient and reversible, and not associated with muscular symptoms.

Several investigational agents for OA (glu-cosamine and chondroitin sulfates, bisphospho-nates and calcitonin) have been attempted and used in practice owing to their structure-mod-

ifying properties, but none has been approved for preventing structural progression of OA, Cooper said.

Strontium ranelate is approved in many countries in Asia for the treatment of postmeno-pausal osteoporosis to reduce the risk of verte-bral and hip fractures.

* SEKOIA: Strontium Ranelate Efficacy in Knee Osteo- arthritis Trial** WOMAC: Western Ontario and McMaster Univer- sities Osteoarthritis Index

9 June 2013 Conference Coverage

Ancient images depict dwarfism

Saras Ramiya

Ancient iconography depicts and identifies different bone disorders in dwarfs accurately, and offers a

unique means of assessing ancient medical notions and collective attitudes.

“Among bone disorders, dwarfism was the most commonly depicted human physi-cal disorder since earliest times on all kinds of media such as tomb reliefs, vase paintings, mosaics and statuary found in Egypt, Greece and the Roman world; they ranged from the Predynastic Period in Egypt – about 3,000 BC to the end of the Roman Empire in the 5th cen-tury AD,” said Dr. Véronique Dasen, associate professor of classical archaeology at the Uni-versity of Fribourg, Fribourg, Switzerland.

The disorders, including hypopituitarism, achondroplasia and hypochondroplasia, were thought to enhance unusual qualities.

Dwarfs were highly respected in ancient Egypt as guardians, especially of childbirth and women, and were associated with the Greek god of revelry, Dionysus. To the Ro-mans, dwarfs were attractive as entertainers.

“[Dwarfism] was never regarded as a dis-ease, but as a sign of special ability and quali-fied dwarfs according to time and place as gods or jesters,” she said.

The pictures provide two types of infor-mation. First, medical – a number of bone disorders can be identified, often accurately, although they are not described in medical treatises. Second, social and religious – each culture developed a unique way of stylizing and selecting relevant features. Every choice on the artist’s part, whether conscious or un-conscious, can reveal how the condition was regarded in the past.

Physical beauty in ancient Egypt, Greece and Rome was defined in terms of propor-tions between the parts of the body. [Dwarfs in Ancient Egypt and Greece. Oxford: Oxford University Press; 1993]

“How did the mind react to those whose appearance did not conform to ideal propor-tions, especially persons suffering from bone deformities?” Dasen queried.

“In this perspective, iconography offers us a unique means of approaching the history of collective attitudes and medical notions.”

European Congress on Osteoporosis and Osteoarthritis 2013, April 17-20, Rome, Italy

10 June 2013 Conference Coverage

Osteocytes key to increasing bone mass

Saras Ramiya

The ability to manipulate osteocyte for-mation holds promise regulating os-teoblast function in skeletal disease,

says Professor Colin Farquharson, chair of skeletal biology at the Roslin Institute, Uni-versity of Edinburgh, UK.

Osteocytes communicate with osteoblasts and osteoclasts to orchestrate bone structure and function, and therefore represent an at-tractive target for the development of diag-nostics and therapeutics for bone diseases, said Farquharson. They make and secrete sclerostin, a potent negative bone mass regu-lator and the first mediator of communication between themselves and osteoblasts and os-teoclasts. Osteocytes can be targeted to pro-mote bone accretion, which would increase bone mass. They may also be used as a posi-tive regulator of bone formation to counter sclerostin’s negative effects.

Farquharson added that strategies to tar-get osteocyte control over osteoblast behavior show promise in reversing age-related de-cline in bone mass and have the added benefit of allowing selective strategies to target the control of osteogenesis.

Mechanical loading, for example, increases osteocyte viability in vitro and contributes to solute transport through the lacuno-canalicular system in bone, which enhances oxygen and nutrient exchange and diffusion to osteocytes.

Skeletal unloading has been shown to induce osteocyte hypoxia in vivo when os-teocytes undergo apoptosis and recruit os-

teoclasts to resorb bone. Microdamage in bone occurs as the result of repetitive events of cycling loading and appears to be asso-ciated with osteocyte death by apoptosis, which appears to secrete a signal to target osteoclasts to perform remodeling at a dam-aged site.

Under normal conditions, osteocytes ex-press high amounts of transforming growth factor (TGF)-β and, thus, repress bone resorp-tion. When bone grows old, the expression levels of TGF-β decrease and the expression of osteoclast-stimulatory factors increases. Bone resorption is then enhanced, leading to net bone loss. [Technol Health Care 2009;17:49-56]

Mechanical stimulation of osteocytes re-leases biochemical signaling molecules, which help maintain the balance between bone for-mation and resorption.

Osteocyte cell death can occur in asso-ciation with pathologic conditions such as osteoporosis and osteoarthritis (OA), which leads to increased skeletal fragility and re-duced ability to sense microdamage and/or signal repair. Oxygen deprivation that oc-curs as the result of bed rest, glucocorticoid treatment and withdrawal of oxygen has been shown to promote osteocyte apopto-sis.

Despite speculation regarding the role of subchondral bone (SCB) in OA pathogenesis, its modified remodeling and thickening con-tribute to the sclerosis that characterizes OA. Many studies pinpoint the prevention of SCB thickening as a potential target for ameliorat-ing OA progression.

European Congress on Osteoporosis and Osteoarthritis 2013, April 17-20, Rome, Italy

11 June 2013 Conference CoverageSignificantly, recent data reveal markedly

reduced osteocyte sclerostin levels in bone from human OA femoral neck, consistent with a dominant role for osteocytes in SCB changes in OA. This places osteoblast-to-

osteocyte transition at center stage as SCB thickening in OA may be restricted by pro-moting osteocyte formation and sclerostin-mediated negative feedback function, Farqu-harson said.

IOF campaign aims to reduce fractures worldwide

Saras Ramiya

The International Osteoporosis Founda-tion (IOF) has launched the ‘Capture the Fracture’ campaign to improve pa-

tient care and reduce fracture-related health-care costs worldwide.

“We’ve had [different approaches] for many years, but the question is … are we ac-tually reducing the incidence of fractures suf-ficiently to decrease the burden of disease in society?” said Dr. Eugene McCloskey, profes-sor of adult bone diseases at the University of Sheffield, Sheffield, UK.

Secondary prevention is the key to reduc-ing the incidence of fractures, he added.

When comparing the distribution of frac-tures in early postmenopausal women with those of fractures 30 to 35 years later, ap-proximately half of the women had a prior fracture. Also, about a third of men with hip fractures had a prior fracture. [Osteoporos Int 2003;14:780-784]

“So, secondary prevention is what we need to address if we are going to succeed in re-ducing the burden of fractures and they are already identifiable in a group of patients,” said McCloskey.

The importance of prior fracture is recog-nized. In risk calculators such as FRAX®, one

of the most important risk factors is prior frac-ture. The risk of subsequent fracture is dou-bled in patients with prior fracture. [FRAX® version 3.7 www.shef.ac.uk/FRAX Accessed 30 April 2013]

Most vertebral fractures are subclinical, presenting on images taken for other rea-sons eg, chest X-rays. Vertebral fractures are an important component for identifying and treating the secondary prevention popula-tion even if the bone mineral density (BMD) is unknown. [Osteoporosis. www.sth.nhs.uk/metabolic-bone Accessed 30 April 2013]

“So, fractures beget fractures – that’s the message. If you have one fracture, you have an increased risk for future fracture,” said McCloskey.

The IOF ‘Capture the Fracture’ campaign aims to cut down the risk of fractures through education, risk assessment and professional support.

12 June 2013 Conference CoverageFirstly, education is important to address

secondary prevention. A review by the IOF fracture group showed that more than half of the programs that looked at reduction in frac-ture risk involved education for patients as well as healthcare providers. [Osteoporos Int 2011;22:2051-2065]

The responsibility of assessing fracture risk and intervening lies in primary care, both

with the patient and with the general prac-titioner, primary care physician or practice nurse. Having a fracture liaison nurse can help in identifying patients at an increased risk of fractures, said McCloskey.

To that end, the ‘Capture the Fracture’ cam-paign facilitates the implementation of coor-dinated, multidisciplinary models of care for secondary fracture prevention.

13 June 2013 Conference Coverage

Personal Perspectives

‘‘ As one of the organizers of this conference, we [the IOF] are happy about it. I think the quality of science at this meeting is getting better year after year. Next year onwards, this conference will become the World Congress on Osteoporosis and Osteoarthritis.

Dr. Dominique D. Pierroz, IOF Science Manager, Switzerland

‘‘ I find this conference interesting in that current knowledge is improving. This is the first time that I am attending this conference. I think this conference is a good example of the multidisciplinary approach to diseases, which is likely to affect all of us. We are learning a lot.

Dr. Innocent Nyaruhirira, Orthopedic Surgeon, Saint-Pierre University Hospital, Brussels, Belgium

‘‘ A lot of scientific evidence was produced at this conference. For example, there is a strong link between muscle and bone. If you have muscle disease, you get bone disease and vice versa. This has been shown at the molecular level as well as the cellular level. As an oncologist, I find that the extent of osteoporosis is underestimated. Women just tolerate it and we do not know how much they suffer.

Dr. Leong Ng, Consultant Physician, Queensland, Australia

‘‘ I am interested in osteoporosis and osteoarthritis, which will be big problems in the population in the near future. With increasing lifespan of people, we are becoming more and more an aged community and we will see more patients with these problems.

Dr. Mohamed Abdel-Wanis, Professor of Orthopedic Surgery, Sohag Faculty of Medicine, Sohag University, Egypt

14 June 2013 Conference Coverage

Hypnosis may benefit patients with chronic pain

5th Association of South-East Asian Pain Societies (ASEAPS) Conference, May 2-5, Singapore

Radha Chitale

Hypnosis can be a useful pain manage-ment tool for patients with chronic pain, according to one expert.

“The basic idea is that although periph-eral activity can influence a person’s expe-rience of pain, it is the brain that creates our experience, including our experience of pain,” said Dr. Mark Jensen, professor and vice-chair for research of the depart-ment of rehabilitation medicine, University of Washington School of Medicine, Seattle, Washington, US. “Interventions that impact brain activity have the opportunity to im-pact brain experience.”

Jensen highlighted the findings of a trial which compared the effects of hypnosis and electromyography (EMG) biofeedback re-laxation training in 37 spinal cord injury pa-tients with chronic pain. [Int J Clin Exp Hypn 2009;57:239-268]

In this study, patients were randomized to either 10 sessions of EMG biofeedback relax-ation, which emphasizes controlling involun-tary stress signals such as heart rate, blood pressure and muscle tension, or 10 sessions of self-hypnosis.

Self-hypnosis involves patients relaxing themselves into the image of a safe place and then imagining experiencing fewer sensa-tions of discomfort or pain and more sensa-tions of relaxation and warmth. They are also prompted that they will be able to experience

this comfort later after a deep breath and that the benefits will last.

Both groups were given an audiotape for practice at home. Both groups reported signif-icant, similar pain reduction following treat-ments – 22 percent of hypnosis patients had at least a 30 percent pain reduction compared with 10 percent of biofeedback recipients – but hypnosis resulted in statistically signifi-cant decreases in daily average pain, which were maintained after 3 months.

Jensen noted that after the 10 treatment sessions 60 percent of hypnosis patients still used their audio recordings and 80 percent used the hypnosis skills they learned daily.

A follow-up study in patients with mul-tiple sclerosis (MS) showed a larger effect on pain intensity with hypnosis than with muscle relaxants. Even though MS pain is

Hypnosis significantly reduced daily average pain compared with electromyography biofeedback in a small study involving spinal cord injury patients with chronic pain.

15 June 2013 Conference Coverageeasy to treat, 47 percent of hypnosis patients responded to their therapy compared with only 14 percent of those receiving muscle re-laxants.

When queried about their continued use of hypnosis skills, patients responded that they felt increased well-being, relaxation and decreased stress, as well as some pain reduc-tion, increased control over pain and a sense of having a new tool for their pain. Some did respond that the therapy did not work, that it was not as effective as they hoped and that the effects did not last.

“Imagine a drug that produces substan-tial decreases in pain ... whose side effects are overwhelmingly positive, including increased sense of well-being and relaxation, [serious]

side effects are rare and at worst they rarely say it doesn’t help or it doesn’t last, and con-tinues to be effective – if you had such a drug, it would be a blockbuster, every patient would be prescribed this drug,” Jensen said.

Layering cognitive behavioral therapy with hypnosis can also successfully help pa-tients improve their pain status through men-tal suggestion and behavioral changes.

Results from hypnosis trials are always variable, Jensen said, and there will be peo-ple for whom the therapy will not work to reduce their chronic pain. Further trials are planned to compare hypnosis with cogni-tive behavioral therapy and to examine the potential for neurofeedback to enhance the benefits of hypnosis.

Pilates a possible pain management toolRadha Chitale

Patients with chronic pain may be wary of exercise but some forms of move-ment, such as clinical Pilates, can alle-

viate symptoms and improve patient condi-tions in the long term, according to Ms. Irene Toh, a physiotherapist at Singapore General Hospital, Singapore.

Pilates can be effective for a variety of chronic pain conditions such as chronic lower back pain, whiplash injuries, fibromyalgia, chronic fatigue syndrome and arthritis.

Patients with chronic pain are unique be-cause normal pain-modulating processes and endogenous analgesics that are triggered with exercise are not accessible to them.

In addition, Toh said chronic pain patients have an altered perception of their body be-

cause of their pain. When asked to describe affected areas they will often refer to them as disproportionately damaged or negative compared with unaffected areas. This percep-

Clinical Pilates can be effective in treating a variety of chronic pain conditions.

16 June 2013 Conference Coveragetion results in exaggerated sensitization, pain and poor movement control, and the result-ing negative feedback can dissuade patients from exercising.

“The focus of Pilates is on good-quality movement and relaxed breathing,” Toh said. “We have the ability to analyze movement and break it down for them to start thinking of the pieces ... Once they see how to do it, they can put it into practice even when they are not in sessions.”

Pilates was developed in Germany by a man named Joseph Pilates in the early 20th century and at the time it was also called con-trology because of its focus on the mind to control muscles.

Clinical Pilates is a subset of Pilates devel-oped in the 1990s. Together with mainstream physiotherapy techniques, clinical Pilates is especially good for rehabilitation for patients with musculoskeletal and neurological condi-tions because it aims to retrain faulty move-ment patterns and improve movement effi-ciency and spinal stability.

The six principles of clinical Pilates are controlled movements, focus on proper form, developing core muscle stability, breathing, flowing movement and precision.

“I want patients to work smarter, not hard-er,” Toh said. “When I progress the patient, I will increase the complexity of movement, not the amount or weight or resistance.”

Research has shown that clinical Pilates is just as effective as regular exercise for im-proving disability, pain, function and health-related quality of life.

One study of patients with lower back pain showed that all participants, who had been randomized to 6 weeks of Pilates (n=44) or general exercise (n=43), improved signifi-cantly and similarly after 12 and 24 weeks, re-spectively, of follow-up. [Med Sci Sports Exerc 2012;44:1197-1205]

Simplicity of instruction and movement, coupled with tactile and visual feedback ,should help reluctant patients begin to exer-cise more, Toh said, which can begin to allevi-ate their chronic pain.

17 June 2013 Conference Coverage

AUA releases new guideline on prostate cancer screening

American Urological Association 2013 Annual Meeting, May 4-8, San Diego, California, US

Elvira Manzano

The American Urological Association (AUA), in its latest clinical practice guideline, recommends against routine

prostate cancer screening of men under age 55 if they are at average risk, a move seen by many as a major departure from the previous guidelines.

For men at higher risk – those with a posi-tive family history or of African-American race – decisions on whether to undergo pros-tate-specific antigen (PSA) testing should be individualized.

The greatest evidence that benefits may outweigh harms of screening appears to be in men between ages 55 and 69, but they should only proceed after careful discussion of the risks and benefits between patients and phy-sicians. “A shared decision-making approach can be used to make the best possible decision about the intervention at the individual lev-el,” said Dr. H. Ballentine Carter from Johns Hopkins Hospital in Baltimore, Maryland, US, and chairman of the panel that developed the guideline. “The AUA has developed de-cision-making tools that patients and physi-cians can use to help in the discussion.”

The guideline also discourages routine screening in men under age 40, those over age 70 or those with less than 10 to 15 years’ life ex-pectancy, given the likelihood that the harms of screening will outweigh risks in these age groups. For men who decide to go ahead with the PSA test, screening should be done every 2 years instead of yearly, Carter said.

The new guideline supercedes the section on prostate cancer detection in the 2009 AUA best practice document which recommended screening at age 40. This time, the recommen-dations were based on evidence from ran-domized controlled trials and not on consen-sus opinion. Another difference, Carter said, is that the evidence was reviewed from an individual perspective and not from a public health perspective. “The point of the guide-line is to help urologists inform an average-risk man who is asymptomatic.”

He added that the AUA guideline was “not a response” to the US Preventative Services Task Force (USPSTF) which recommended against the routine use of the PSA test on the assertion that there is more harm to it than any benefit.

The PSA test supposedly poses no physical risk to patients as it was based on a simple blood draw; however, it can result in false-positives and overdiagnosis which have seri-ous consequences.

“It is time to reflect on how we screen men for prostate cancer and take a more selective approach in order to maximize benefit and minimize harms,” Carter said.

The new guideline, announced during the 2013 AUA annual meeting in San Diego, Cali-fornia, mainly focused on the efficacy of PSA screening for early prostate cancer detection with the intent to reduce prostate cancer mor-tality. Use of secondary tests to determine the need for prostate biopsy was not considered by the guideline panel. Focus was also limited to asymptomatic men.

18 June 2013 Conference Coverage

Prostate cancer: Less LUTS after prostatectomy

American Urological Association 2013 Annual Meeting, May 4-8, San Diego, California, US

Radha Chitale

Men with prostate cancer who under-go radical prostatectomy may have reduced lower urinary tract symp-

toms (LUTS) as they grow older, according to a study.

“Our findings suggest that the most impor-tant contributor to LUTS in the aging male is the prostate,” said researchers from New York University in New York, US. “Preventing the progression of LUTS is an unrecognized ad-vantage of radical prostatectomy.”

LUTS is known to progress as men age and research shows that radical prostatectomy improves LUTS in patients who already have clinically significant LUTS.

The researchers culled data from nearly 2,000 men who underwent radical prostatec-tomy under the care of one surgeon from Oc-tober 2000 to September 2012. Patients com-pleted the American Urological Association Symptoms Score (AUASS), which tracks the severity of urinary symptoms, through 120 months of follow-up.

Men with few LUTS symptoms exhibited a transient spike postoperatively that settled back down to baseline levels within 2 years and remained stable during the follow-up period.

Average AUASS before prostatectomy was about 7 (mild), before increasing to 8.5-9 (moderate) postoperatively, then returning to baseline.

The researchers controlled for age, pros-tate-specific antigen levels, Gleason score,

cancer severity, surgery type, race and marital status.

Men with clinically significant LUTS prior to surgery also experienced a spike in symp-toms postoperatively, but it also declined within several months and did not increase again for the duration of follow-up or show signs of age-related progression.

“The present study is the longest report-ed longitudinal assessment of LUTS follow-ing radical prostatectomy,” the researchers said. “Elucidating the natural history of LUTS in men with prostate cancer follow-ing radical prostatectomy provides insights into the role of the prostate in LUTS pro-gression.”

A largely unrecognized advantage of radical prostatectomy is that it helps prevent the progressions of LUTS.

19 June 2013 Conference Coverage

Regular exercise protects men against sexual dysfunction

American Urological Association 2013 Annual Meeting, May 4-8, San Diego, California, US

Rajesh Kumar

Regular physical exercise protects mid-dle-aged men against sexual dysfunc-tion, and the degree of risk reduction

is directly correlated with the intensity and duration of exercise, a new study shows.

Men should, therefore, be counseled on the type and duration of exercise that may pro-tect them against sexual dysfunction, said re-searcher Dr. Erin McNamara of Durham VA Medical Center in Durham, North Carolina, US, and colleagues.

Previous studies have observed improve-ment in sexual function scores in men follow-ing weight loss secondary to diet and exer-cise. The researchers hypothesized that men with higher exercise level would have higher sexual function scores and set out to define the type and duration of exercise that would be protective against sexual dysfunction.

They recruited 167 healthy men (median age 62 years, BMI 30 kg/m2) at the Durham VA Medical Center who completed the UCLA prostate cancer index (UCLA PCI) sexual function survey, which includes six sexual function questions: ability to have erection, ability to reach orgasm, quality of erection, frequency of erection, overall sexual function and bother.

These answers were converted to a numer-ic score on a 0 to 100 scale, and averaged into an overall sexual function score with higher scores equating to higher function. Median sexual function in participants was 50 points.

The participants were also asked to com-plete the leisure score index (LSI) of the Godin leisure-time exercise questionnaire (GLTEQ) regarding current exercise behav-ior, and were asked average frequency and duration of mild, moderate and strenuous intensity exercise in a typical week. Total current exercise was calculated in terms of metabolic equivalent task (MET) hours per week.

After adjusting for age, race, BMI, heart disease, diabetes and depression, men who reported more MET hours per week of exer-cise had significantly higher sexual function scores [p<0.001]. For each 1-hour-per-week in-crease in mild exercise, the risk of sexual dys-function decreased by 18 percent [OR=0.82, p=0.003]. For the same amount of moderate exercise, the risk was reduced by 28 percent and for strenuous activity it was reduced by 44 percent.

A US study has shown that weekly exercise duration and intensity is positively correlated with sexual function in men.

Golden Gate Bridge

MIMS.com now comes with a brand new look and mobile app!Along with a redesign that helps enhance ease of access to crucial

clinical information, MIMS.com can now be accessed through a FREE mobile application, available on the iTunes store.

With MIMS available across multiple platforms and devices, you can

now easily and conveniently find the most up-to-date and relevant drug

information anytime, anywhere.

www.mims.com MIMS mobile/tablet app facebook.com/mimscom

CONNECT WITH MIMS:

Journal of Paediatrics, Obstetrics & Gynaecology

21 June 2013 Expert Opinion

Premature ejaculation negatively impacts relationships

Professor Ganesh AdaikanClinical Sexologist National University Hospital Women’s Centre Singapore

Premature ejaculation is the most common sexual dysfunction in men [European Association of Urology:

Guidelines Male Sexual Dysfunction: Erec-tile dysfunction and premature ejacula-tion. [Internet] 2013 Mar [cited 2013 Mar 8]. Available from: www.uroweb.org/fileadmin/guidelines/2012_Guidelines_large_text_print_total_file.pdf], but is under-detected, under-diagnosed and under-treated. Aside from being a medical condition, premature ejaculation can also lead to significant con-sequences on the emotional well-being and overall quality of life of both men and their partners because of the frustration and dis-appointment resulting from poor sexual sat-isfaction.

In one of the largest studies of premature ejaculation ever conducted, the Asia Pacific Premature Ejaculation and Erectile Dysfunc-tion Prevalence and Attitudes study, it was found that up to one in three men in the re-gion have some form of premature ejacula-tion. [J Sex Med 2012;9:424-465]

This study aimed to evaluate prema-ture ejaculation prevalence and the impact of premature ejaculation. The 48-question survey interviewed nearly 5,000 men aged 18-65 years from nine countries; Austra-lia, China, Hong Kong, Indonesia, Korea,

Malaysia, New Zealand, Taiwan, Thailand and the Philippines. The survey was con-ducted using the five-item Premature Ejacu-lation Diagnostic Tool (PEDT), a validated instrument for diagnosing premature ejacu-lation. [Eur Urol 2007;52:565-573]

In general, men with premature ejacula-tion experienced low levels of sexual satis-faction and high levels of frustration over their control over ejaculation, with only 45 percent of respondents with premature ejac-ulation reporting that sexual intercourse was satisfactory for them most of the time or al-ways. Among respondents with premature ejaculation, 57 percent reported that they ejaculated before they wished, 79 percent felt frustrated because of ejaculation before they wanted to, and 86 percent were concerned that they may have left their partners sexu-ally unfulfilled. [J Sex Med 2012;9:424-465]

A similar pattern of results was observed in a random sample of 243 men in Singapore, aged 18 to 55 years. In this study, the PEDT results showed that 34 percent of the respon-dents had some form of premature ejacula-tion, and among respondents diagnosed with premature ejaculation, at least 79 per-

Premature ejaculation may cause one or both partners to feel sexually dissatisfied.

22 June 2013 Expert Opinioncent frustrated due to ejaculating before they wished it to happen. In addition, 46 percent of respondents with premature ejaculation admitted to having discussed the problem with their partners, with the most common motivation to do so involving a sense of let-ting the partner down (43 percent). [J Men’s Health 2011;8(Suppl 1):S84-S86]

A satisfying sex life is an essential part of a successful relationship, and sexual dissat-isfaction arising from premature ejaculation can negatively impact a couple’s intimacy and relationship, and ultimately reduce their overall quality of life. [Health Qual Life Out-comes 2008;6:33, J Urol 2007;177:1065-1070]

Greater awareness of premature ejacula-tion and the impact of the condition needed so that men and their partners do not feel stigmatized. They should feel encouraged to take action and to speak to their physicians. At the same time, physicians should proactively approach the subject with their patients, and utilize simple and validated diagnostic tools such as the PEDT to assess patients.

There are several treatments for prema-ture ejaculation, including dapoxetine, an on-demand oral medication that is the first and only prescription drug specifically de-veloped and approved for the treatment of premature ejaculation. Men should speak to their physicians about available treatments that can improve control over ejaculation and sexual satisfaction for themselves and their partners. It may also help for couples to undergo counselling to relieve performance anxiety and to discuss mutually effective ways to cope with the stress of a decreased level of satisfaction in their sexual relation-ship.

Through open communication, men will realize that premature ejaculation is a medi-cal condition that can be successfully treated. With improved control over ejaculation, men with premature ejaculation and their part-ners can look forward to better sexual satis-faction and consequently, an improved rela-tionship and quality of life. [Health Qual Life Outcomes 2008;6:33]

About the author Professor Ganesh Adaikan is a clinical sexologist at the Andrology Clinic at Singapore’s National University Hospital (NUH) Women’s Centre and Research Professor at the Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore.

23 June 2013 News

Laura Dobberstein

The use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression in expectant mothers has

been shown to have no adverse effects on in-fant growth during the first year of life, says a recent US study.

“Consideration of the impact of both ante-natal SSRI and depression exposures on fetal and infant growth is an understudied com-ponent of the risk-benefit decision process for developing treatment plans for depressed pregnant women,” said study author Dr. Katherine Wisner, director of the Asher Cen-ter for the Study of Depression at Northwest-ern University Feinberg School of Medicine, Chicago, Illinois, US, and colleagues.

The longitudinal observational study in-cluded 238 pregnant women, of whom 97 did not have depression and were not taking SSRI medication, 46 had depression and were tak-ing an SSRI, and 31 had depression but were not taking an SSRI. The expectant mothers were assessed at 20, 30 and 36 weeks’ gestation and the infant and mother were examined at 2, 12, 26 and 52 weeks after birth. The researchers found that 20 percent of those receiving SSRIs gave birth prematurely compared with 10 per-cent of those in the depressed, non-medicated group, and 5 percent of those in the group that was neither depressed nor medicated [Am J Psychiatry 2013;170:485-493].

However, SSRI use and depression did not significantly affect infants’ weight, length and head circumference at any point during the first year of life.

SSRI use in pregnancy: No link to birth, growth problems

Antenatal SSRI use has previously been implicated in adverse pregnancy outcomes such as miscarriage and infant growth problems.

“Pregnant women often discontinue both psychotherapy and pharmacotherapy and do not resume care after birth,” said Wisner and colleagues. Past studies have shown that preg-nant women who stop taking SSRIs around con-ception have a 68 percent relapse rate compared with a 26 percent relapse rate in those who con-tinue treatment. [JAMA 2006;295:499-507]

“This is the reason that pregnant women are treated with pharmacotherapy; that is, the anticipated overall benefit is greater than the risk,” said the study authors.

The Medical Tribune spoke to Singapore-based physician Dr. Cornelia Chee, director and senior consultant at the Women’s Emo-tional Health Service at the National Univer-sity Hospital, Singapore. “SSRIs have been implicated in adverse outcomes such as in-creased miscarriage and malformation rate, the development of persistent pulmonary hypertension of the newborn and neonatal adaptive syndrome,” said Chee.

“This [latest] study goes some way towards answering some of the many questions regard-ing the safety of SSRI use in pregnancy,”she said.

24 June 2013 News

Beer buzz begins with taste

Laura Dobberstein

The taste of beer alone can prompt a release of dopamine in the brain and stimulate cravings for the beverage.

This was the main finding of a study which scanned the neurologic responses of a sample of men drinking their favorite beer using positron emission tomography (PET) imaging technology.

“The primary findings of the investigation indicate that the taste of a preferred alcoholic drink (beer), absent a pharmacologically sig-nificant dose of alcohol, is capable of induc-ing relative increases in dopamine transmis-sion in the brain’s ventral striatum,” wrote study author Dr. David A. Kareken, profes-sor of neurology at the Indiana University School of Medicine in Indianapolis, Indiana, US, and colleagues.

In the study, participants reported an increased desire to drink beer over a well-known sports drink (Gatorade®) and PET scans showed an increase in dopamine ac-tivity after tasting only 15 mL of beer over a 15-minute period of time. These results oc-curred despite study participants ranking Gatorade® as more pleasant than beer. The effect was more pronounced in those with a family history of alcoholism. [Neuropsycho-pharmacology 2013; doi:10.1038/npp.2013.91]

Fourty-nine male drinkers in good phys-ical and mental health underwent two PET scans. One scan was completed while tast-ing the participant’s most frequently con-sumed brand of beer and another was deliv-ered while tasting Gatorade®. The amount of beer distributed to the study participant

was not enough to intoxicate. The men rated the pleasantness and intensity of the drink and their desire to have more of the beverage.

“This is a very interesting study showing for the first time that the flavor of beer, in-dependent of its pharmacologic effects, in-duces increased activity in the brain’s reward centers,” Dr. Juan Dominguez, principal in-vestigator at the Neuroendocrinology and Motivation Laboratory in the Department of Psychology at the University of Texas, Aus-tin, Texas, told the Medical Tribune.

Dominquez explained that increases in-dopamine in the regions of the striatum are associated with reward and sensations of feeling good. Eating, sexual activity and drugs like cocaine or alcohol are all linked to increases in dopamine.

“What is most interesting in this study is that the flavor of alcohol alone elicited this neurological response, and that the response was greatest in individuals with first-degree alcoholic relatives, which suggests a genet-ic predisposition to this response,” added Dominquez.

The researchers did not see a statistical difference in drinks per week between those with and those without a family history of alcoholism, and suggested future research to explore family history and drinking interac-tion.

Dominguez warned that the study should be approached with caution because it is the first of its kind. “Additional studies will more clearly elucidate on the mechanisms respon-sible for this increased response to the taste of beer.”

25 June 2013 News

Rajesh Kumar

Women who have migraines with aura (MwA) may be more likely to have cardiovascular (CV) prob-

lems, and those on newer contraceptives may be at higher risk for blood clots, according to two large studies.

The first prospective cohort study showed that MwA is a strong contributor to the de-velopment of major CV events such as heart attack and stroke. The Women’s Health Study involved 27,860 women aged ≥45 who were free of CV disease at baseline, and self-re-ported information on migraine and lipid levels. [Neurology 2013;80 (Meeting Abstracts 1):S40.001]

At baseline, 5,130 women reported mi-graine, of whom 1,435 reported MwA. Dur-ing 15 years of follow-up, there were 1,030 cases of heart attack, stroke or death from a CV cause (overall incidence rate [IR], 2.4 per 1,000 women per year (95% CI 2.3-2.6).

The researchers examined the relative contribution of various vascular risk fac-tors to these major CV events. After having a systolic blood pressure of ≥180 mmHg ad-justed IR=9.8 (6.9-13.9), MwA was the sec-ond strongest single contributor to major CV risk (IR=7.9; 6.2-10.0) followed by diabetes (IR=7.1; 5.6-8.9), family history of prema-ture myocardial infarction (IR=5.4; 4.5-6.5), current smoking (IR=5.4; 4.6-6.4), and body mass index ≥35 kg/m2 (IR=5.3; 4.0-7.2).

“After high blood pressure, MwA was the second strongest single contributor to risk of

Migraines with aura linked to CV risk in women

Women with MwA can reduce their CV risk through positive lifestyle changes.

heart attacks and strokes,” said lead author Dr. Tobias Kurth of INSERM, the French Na-tional Institute of Health and Medical Re-search in Bordeaux, France, and Brigham and Women’s Hospital in Boston, Massachu-setts, US.

“It came ahead of diabetes, current smok-ing, obesity and family history of early heart disease,” said Kurth.

He cautioned that while such women have an increased risk, it does not mean that ev-eryone with MwA will have a heart attack or stroke. They can reduce their risk in the same ways others can, such as not smoking, keep-

26 June 2013 Newsing blood pressure low and weight down, and exercising, he added.

The second study looked at the occurrence of blood clots in women with migraine who took hormonal contraceptives. The study involved women with migraine with and without aura who were taking both older and newer contraceptives (the contraceptive patch and ring). Of the 145,304 women who used the contraceptives, 2,691 had MwA and 3,437 had migraine without aura. [Neurology 2013;80 (Meeting Abstracts 1):S40.002]

Women with MwA were more likely to have experienced blood clot complications such as deep vein thrombosis (DVT) with all types of contraceptives than women with mi-graine without aura.

For example, 7.6 percent of women with MwA who used a newer generation com-bined hormonal contraceptive had DVT com-pared with 6.3 percent of women with mi-graine without aura, but the timing of the two events was not clear. The incidence of blood clot complications was also higher in women with migraine who took contraceptives than women taking the contraceptives who did not have migraine.

Women who have MwA must include this information in their medical history and talk to their doctors about the possible higher risks of newer contraceptives given their con-dition, said study author Dr. Shivang Joshi of Brigham and Women’s Falkner Hospital in Boston, Massachusetts, US.

27 June 2013 News

Laura Dobberstein

Meeting a physician for a follow-up appointment is associated with a reduction in the risk of heart attack

or death in high-risk patients who presented to an emergency room (ER) for chest pain within the past month, according to a recent study.

“Assessment of chest pain is one of the most common reasons for emergency depart-ment visits in developed countries,” said the study authors, led by Dr. Dennis T. Ko of the Institute for Clinical Evaluative Sciences in Ontario, Canada.

Current guidelines recommend that a pa-tient see a physician for follow-up after ER visits for chest pain. However, little has been known about how such visits impact patient prognosis.

The researchers studied 56,767 patients who were diagnosed in an ER with chest pain between April 2004 and March 2010. All pa-tients were considered high-risk, meaning they had previously been diagnosed with heart disease or diabetes. The patients were discharged from the hospital and had no ad-verse outcomes by day 30 post-discharge. [Circulation 2013;127:1386-94]

In the 30 days following their ER stay, 25 percent had no physician follow-up, 58 per-cent were evaluated by primary care physi-cians alone and 17 percent were evaluated by cardiologists. Those seen by cardiologists received the most diagnostic testing, medical therapy and coronary revascularization, like bypass or stent procedures.

Despite being the group with the most car-diac risk factors, previous cardiac procedures

Follow-up crucial for high-risk ER chest pain patients

and cardiac comorbidities, those who saw a cardiologist had the best results.

“A cardiologist is a specialist that treats heart disease in all of its forms. We see more patients with this disease and are more fa-miliar with the progression of the disease and how to treat it,” Dr. Ted Tyberg, board-certified cardiologist affiliated with New York Presbyterian Hospital, told Medical Tribune.

Those who saw a cardiologist were 21 per-cent less likely to have a heart attack or die within 1 year than those who did not have fol-low-up care, and 15 percent less likely to have a heart attack or die within 1 year than those who saw a primary care physician alone.

“It is always important to immediately follow up with your physician after a hospi-tal stay,” said Tyberg, who was named a top cardiologist by New York Magazine. “No one knows you better than your doctor; your his-tory, your medications, your other medical conditions.”

The researchers speculated that patients may not be seeking care because they did not know they needed a follow-up or were not re-ferred to a specialist or physician that could provide care. Others may not have sought care because of additional costs.

Future research could examine economic factors that lead patients to not seek care.

“As physicians, we are often so focused on knowing which drug to prescribe or which test to order that we overlook the fact that many patients fail to get follow-up care to begin with,” added Ko. “Patients need to advocate for themselves and physicians need to be more diligent about arranging follow-up care.”

28 June 2013 News

Laura Dobberstein

An increase in dietary fiber intake may decrease risk of a first-time stroke, ac-cording to a meta-analysis performed

by researchers in the UK. “Stroke is the leading cause of disability in

many developed countries, and its primary prevention should, therefore, be a key public health priority,” wrote the study authors, led by Ms. Diane Threapleton, a Ph.D. candidate at the University of Leeds’ School of Food Sci-ence & Nutrition in Leeds.

A diet rich in fiber is already known to reduce a patient’s chances of key stroke risk factors like hypertension and high choles-terol.

“Most people do not get the recommended level of fiber,” said Threapleton. The Ameri-can Heart Association (AHA) recommends at least 25 g of fiber per day. This amounts to six to eight servings of grain and eight to 10 serv-ings of fruits and vegetables.

Threapleton and her team searched exist-ing databases for studies reporting fiber in-take and ischemic or hemorrhagic stroke in-cidence between January 1990 and May 2012. They found eight observational studies from the US, northern Europe, Australia and Japan including a total of 327,537 adults who were healthy at the start of their respective study. [Stroke 2013;44:1360-1368]

The researchers found that a 7 g increase in total daily fiber intake was linked to a 7 percent decrease in first-time stroke risk. The study authors noted that a 7 g increase was an achievable goal equivalent to adding a por-tion of whole-meal pasta, a piece of fruit such as apple, pear or orange, and a serving of to-matoes to the diet each day.

Benefits varied depending on type of fiber. Water-soluble fiber, found in beans, nuts, veg-etables and psyllium husk, reduced the risk significantly, while insoluble fiber, found in whole grains, vegetables and cereals, reduced the risk slightly.

Water-soluble fiber increases feelings of sa-tiety by forming gels in the stomach and small intestine that slow down the rate of nutrient absorption and gastric emptying. Because fi-ber can cause these feelings of fullness, less food is eaten, thereby, attenuating or prevent-ing weight gain and reducing other risk fac-tors for stroke.

Dietary fibers also reduce the risk of stroke by improving insulin resistance and regulat-ing blood cholesterol levels.

A lack of data on fiber from different foods prevented the researchers from making further conclusions about fiber type and stroke. “There is a need for future studies to focus on fiber type and to examine risk for ischemic and hem-orrhagic strokes separately,” said Threapleton and colleagues.

Fiber-rich diet lowers risk of first-time stroke

29 June 2013 News

New diagnostic options for HCC and cholangiocarcinoma in the pipeline

Pank Jit Sin

Urinary metabolites may soon be used as markers to diagnose hepatocel-lular carcinoma (HCC) and cholan-

giocarcinoma (CC), according to results from two clinical trials.

In the trial involving HCC, which was car-ried out in West Africa on the case-control platform of Prevention of Liver Fibrosis and Carcinoma in Africa (PROLIFICA), patients with HCC, cirrhosis, non-cirrhotic liver dis-ease and healthy controls had their urine samples analyzed with urinary nuclear mag-netic resonance (NMR). Multivariate analy-ses of the spectra showed distinct profiles for urine samples of patients with HCC com-pared to those with cirrhosis, non-cirrhotic liver disease and healthy controls with a sensitivity of 87- , 86- and 97 percent, respec-tively.

The sensitivity of NMR suggests that a person’s urinary metabolite profile is more accurate than serum alfa-fetoprotein (AFP) in determining HCC status. The serum AFP profile is accurate to 79-, 75- and 76 percent in detection of those with cirrhosis, non-cir-rhotic liver disease and normal patients, re-spectively.

The telltale signs of HCC were increased metabolites such as methionine, acetylcarni-tine, carnitine, N-acetylglutamate, 2-oxoglu-tarate and indole-3-acetate (p<0.001). Creatine was significantly lower in HCC samples com-pared with controls.

European Association for the Study of the Liver (EASL) general secretary Professor Mark Thurz said the findings would be wel-comed by physicians as they “validate uri-nary metabolic profiling as a potential screen-ing tool for HCC, with superior diagnostic accuracy to serum AFP.”

In another (unrelated) Phase II trial, it was demonstrated that a combined bile and urine proteomic test increased the diagnostic accu-racy of CC in patients with biliary strictures of unknown origin.

The investigators had recently established diagnostic peptide marker models in bile and urine to detect local and systemic altera-tions during CC progression. This achieved, they then combined both models in order to achieve a higher degree of diagnostic ac-curacy. The result was a CC-diagnostic ac-curacy level of more than 90 percent, which was “most applicable for patients with biliary strictures of unknown origin referred to en-doscopy.”

30 June 2013 NewsThursz said the bile and urine findings

could substantially improve diagnosis of CC and may lead to early therapy and improved prognosis. He said both data sets (for HCC and CC) demonstrated the increasing value of proteomic and metabonomic techniques. If the findings are collaborated by further

investigation, a simple urine-dipstick test could be all that is needed to diagnose HCC and CC.

Both the HCC and CC study results were presented at the International Liver Con-gress™ 2013, held in Amsterdam, The Neth-erlands, recently.

Prenatal use of anti-epilepsy drug may raise autism risk

Malvinderjit Kaur Dhillon

The use of valproate, a drug prescribed for the treatment of epilepsy and other neurophyschological disorders, dur-

ing pregnancy has been linked to an increased risk of autism in offspring, a Danish study shows. [JAMA 2013;309(16):1696-1703]

Exposure to anti-epileptic drugs during pregnancy had been previously linked to an increased risk of congenital malformation and delayed cognitive development in the offspring. However, very little was known of the risk anti-epileptic drugs pose for other se-rious neuropsychiatric disorders.

Dr. Jakob Christensen, a consultant neu-rologist at Aarhus University Hospital, Den-mark, and colleagues studied the association between maternal use of valproate during pregnancy and the risk of autism spectrum disorder and childhood autism in offspring. The population-based study involved all chil-dren born in Denmark between 1996 and 2006.

The researchers used national registers to identify children who were exposed to val-proate during pregnancy and subsequently

diagnosed with autism spectrum disorders, which included childhood autism (autistic disorder), Asperger syndrome, atypical au-tism and other or unspecified pervasive de-velopmental disorders.

The data was adjusted for factors that might influence outcomes such as maternal and pater-nal age at conception, parental psychiatric his-tory, gestational age, birth weight, sex, congeni-tal malformations and parity. The children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration or December 31, 2010, whichever came first. Data from 655,615 children was studied.

Through the duration of the study, 5,347 children were diagnosed with autism spec-trum disorder, including 2,067 with child-hood autism. A group of 2,644 children was identified as exposed to antiepileptic drugs during pregnancy. This included 508 children who were exposed to valproate. Results from the study showed the use of valproate during pregnancy was linked with an absolute risk of 4.42 percent for autism spectrum disorder and an absolute risk of 2.5 percent for child-hood autism.

31 June 2013 NewsThe researchers found that children of

women who used valproate during pregnan-cy had a higher risk of autism spectrum dis-order and childhood autism compared with children of women who did not use valpro-ate. Their risks were also higher in children of women who were previously treated with valproate, but who stopped using the drug just before their pregnancy.

“Because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance. Still, the absolute risk of autism spectrum disorder was less than 5 per-cent, which is important to take into account when counseling women about the use of val-proate in pregnancy,” the researchers wrote.

White fat, brown fat, same fatPank Jit Sin

The two types of fat cells in mammalian organisms – white and brown – have been shown to convert between the two

forms, according to scientists at the Swiss Fed-eral Institute of Technology (ETH) in Zurich.

White fat cells (adipocytes) are energy stores which are filled in times of calorie excess. The fat in these cells are kept in the form of lipid droplets, which are mobilized during energy scarcity. At the other end of the spectrum are what are known as brown adipocytes, which produce heat by burning fat and sugar to release energy. This mecha-nism is utilized by newborn babies to regulate body temperature. [Nature Cell Biology 2013, Advance Online Publication, DOI: 10.1038/ncb2740]

As brown fat cells easily lose their mass when converted into energy, the increase of brown adipocyte numbers and activity in hu-mans would, theoretically, allow us to burn off excess calories and lose weight.

Contemporary belief is that brown adi-pocytes reduce in numbers as an organism grows. However, it was recently shown that

brown adipocytes also exist in human adults and that these adipocytes are formed from white fat deposits in response to cold temper-atures. These cells are termed ‘brite’ (brown-in-white).

Christian Wolfrum, a professor at the In-stitute of Food, Nutrition and Health, and his team of researchers generated mice that allowed them to genetically label specific fat cells.

The mice were then kept in various envi-ronments – 8°C for a week, followed by sev-eral weeks in normal room temperature. The team observed the formation of brown adi-pocytes from existing white fat deposits – a process they called ‘britening.’ The process was reversible, and after a few weeks of warm adaptation, the brown adipocytes reverted to white again. What this means is that brite cells are less common in warmer climates than in colder ones.

The researchers concluded that since hu-mans have similar cells as mice, the same processes should occur in humans upon cold stimulation. Wolfrum said new strategies to convert white adipocytes into brown ones could potentially help in the treatment of obesity.

Essential Clinical Practice Toolkit

On-The-Go

The FREE MIMS app delivers critical prescribing information, medical news and CME articles as well as clinical calculators essential to physicians’ daily practice needs.

With MIMS available across multiple platforms and devices, you can now easily and conveniently find the most up-to-date and relevant drug information you need anytime, anywhere.

Join over a million MIMS members who have incorporated MIMS into their daily workflow. Connect with MIMS today.

www.mims.com MIMS mobile/tablet app facebook.com/mimscom

MIMS-IOS206x276_0513.indd 1 5/23/13 4:37 PM

33 June 2013 In Practice

Managing dengue fever in primary care

Dr. Jenny LowSenior Consultant Department of Infectious Diseases Singapore General Hospital Singapore

Dengue fever is a mosquito-borne in-fection caused by the dengue virus, the most common mosquito-borne

viral infection in the world. We no longer talk about dengue as a disease affecting Asian countries – at least 40 percent of the world’s population is at risk for dengue because of where they live and their exposure to the vi-rus from mosquito bites.

In Singapore, dengue is endemic. There is a baseline infection rate but epidemics with in-creased cases tend to happen every 5-6 years. The disease is also more prevalent in the hotter months.

Primary care doctors probably play the big-gest role in identifying and caring for patients with dengue fever. Most of the time patients will go to their family doctor to seek medical

advice first, as the symptoms of early dengue infection cannot be differentiated from other viral illnesses. If dengue is suspected, non-ste-roidal anti-inflammatory drugs and intramus-cular injections should be avoided due to the risk of bleeding. The family physician should monitor the patient regularly throughout the

course of illness if dengue is suspected. If the doctor is concerned that patient may be at risk for severe dengue, the doctor should then re-fer the patient to hospital for further medical evaluation.

Dengue fever runs its own courseDengue fever is a self-limiting illness. Once

a person is bitten by a virus-carrying mosquito, he or she will come down with flu-like symp-toms after an incubation period of 3-7 days. The patient may experience high fever, body aches and pains, loss of appetite and, in some cases, nausea and vomiting. Most patients will recover from the infection after about a week of illness.

One of the hallmarks of dengue fever occurs around day 4-5 of illness – the fever begins to improve but the blood platelet count starts to fall. This might cause patients to present with petechial rashes, which are small capil-lary bleeds just under the skin which look like small red dots. They are harmless but can be alarming and usually send patients back to the doctor who, under suspicion of dengue fever, would refer the patient to a hospital or poly-clinic for a blood test.

Depending on how low the platelet levels are, and if the patient is otherwise well (if they are young, healthy, and able to drink sufficient fluids), they can be sent home and instructed to rest. Polyclinic doctors can continue to mon-itor the patient without referring to a hospital.

However, if the platelets are low and the pa-tient is unwell, has poor appetite, is not able to drink sufficient fluids, or if there is a worry of dengue complications that may result in se-vere dengue, doctors may refer the patient to hospital for further management.

Primary care doctors probably

play the biggest role in identifying

and caring for patients

with dengue fever

‘‘

34 June 2013 In PracticeSevere dengue causes plasma leaks and bleeding

The most important thing about dengue vi-rus is its ability to cause severe disease. It is not well understood how the virus interacts with the cell lining of blood vessels but in severe dengue, plasma leaks into the surrounding tis-sues and accumulates. Fluid can accumulate in the lungs as well, resulting in hypotension and shock if the person does not receive fluid resuscitation in time.

The other feared complication is bleeding. Bleeding can occur in the gut, gums, urinary tract and brain. Women may also experience heavy menstrual bleeds.

Patients over 65, those with other medical conditions such as diabetes, pregnant women and young children may be at risk for more se-vere forms of dengue infection. However, who is at risk for bleeding is not well understood.

Some other clues that a patient might be experiencing severe dengue include restless-ness, abdominal pain, persistent vomiting, and bleeding of the gums or blood in the vomit or stool. These are important symptoms for a pri-mary care doctor to look out for to decide if a patient can be sent home to rest or come to hospital attention. If in doubt, medical practi-tioners should refer the patients to the hospital for further assessment.

No ‘magic bullet’ for dengue There is no curative treatment for dengue

infection. Rather, medications are given to alle-viate the signs and symptoms. Aspirin should not be given to patients. It can cause severe

bleeding. Paracetamol is usually prescribed to relieve fever, muscle and joint aches and headache. Bed rest is essential and the patient should consume plenty of water which will help to alleviate the illness.

In general, dengue fever is self-limiting. Death rarely occurs in severe cases and most developed countries have trained medical per-sonnel and proper care facilities to manage severe disease. The fatality rate is less than 1 percent in such countries.

Theoretically, a person may contract den-gue fever four times as there are four different serotypes of virus. It is not uncommon to get dengue fever at least twice in a lifetime for peo-ple living in endemic areas. However, patients cannot fall ill with the same serotype twice as they will have developed antibodies against that serotype.

The only method of dengue virus control known to be effective is to stop the breeding of

Paracetamol is usually prescribed

to relieve fever, muscle and

joint aches and headache

‘‘

35 June 2013 In Practicethe Aedes aegypti mosquito, the dengue virus vector. When outbreaks occur, primary care doctors may be more alert to the possibility of dengue diagnosis based on patient’s complaints.

Conclusion Dengue fever is the most common mosquito

borne viral infection worldwide. Most of the time, it is a self-limiting illness though its presen-tation cannot be differentiated from other viral illnesses. Severe dengue can occur in a subgroup

of patients at high risk and is characterized by plasma leakage and/or bleeding. It is important to recognize the symptoms of severe disease early so that patients can be referred for proper medical care at the critical stages of illness to pre-vent complications and death. Disease manage-ment is symptomatic and there is no vaccine to prevent infection nor is there a proven effective drug to treat acute dengue fever. Prevention and control is best done environmentally through vector control.

Online Resources:

World Health Organization www.who.int/topics/dengue/en DengueNet http://apps.who.int/globalatlas/default.asp Singapore Dengue Infectious Disease Bulletin www.dengue.gov.sg US Centers for Disease Control and Prevention www.cdc.gov/dengue

36 June 2013 Research Reviews

β-Blockers in heart failure

β-Blockers are effective in the treatment of heart failure with reduced ejection fraction, but it is not known whether all

β-blockers are similarly effective – a class effect. A network meta-analysis has shown this to be the case.

The analysis included 21 randomized trials (23,122 patients) in which atenolol, bisoprolol, bucindolol, carvedilol, metoprolol or nebivolol were compared with standard treatment or placebo for patients with heart failure and reduced ejection frac-tion. β-Blockers were associated with a significant reduction in mortality of 31 percent after 12 months. There were no significant differences between individual β-blockers as regards overall mortality, sudden cardiac death, death from pump failure, rates of drug discontinuation or improvement in ejection fraction.

The beneficial effect of β-blockers in heart failure with reduced ejection fraction appears to be a class effect.

Chatterjee S et al. Benefits of β-blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 2013;346:13(f55); Mentz RJ. β-Blockers for heart failure: which works best? Ibid: 8 (f480) (editorial).

Calcium intake and mortality in Swedish women

Meta-analyses of randomized studies have shown that taking calcium supplements is associated with increased risk of coronary disease and stroke. A Swedish cohort study has confirmed the increased risk for cardiovascular disease in general, but not for stroke.

The Swedish mammography cohort was set up in 1987 and included 61,433 women born between 1914 and 1948. National registries provided data about all-cause and cardiovascular mortality over a mean follow-up of 19 years. Food frequency questionnaires in 1987 and 1997 provided data about dietary intake and use of calcium supplements for 38,984 women. The relationship between calcium intake and all-cause mortality took the form of a ‘J-shaped curve’ with higher mortality at both extremes of intake. An intake of 1,400 mg a day of calcium was associated with significant increases of 40 percent in all-cause mortality, 49 percent in cardiovas-cular mortality, and 114 percent in coronary disease mortality, and no significant change in stroke mortality, compared with a calcium intake of 600-1,000 mg a day. After further statistical analysis, low intakes of calcium (<600 mg/day) were no longer significantly associated with increased mortality. Among people taking calcium tablets and with a dietary calcium intake of >1,400 mg/day, all-cause mortality increased 2.6-fold.

High calcium intake is associated with increased all-cause and cardiovascular mortality.

Michaëlson K et al. Long-term calcium intake and rate of all cause and cardiovascular mortality: community-based prospective longitudinal cohort study. BMJ 2013;346:14 (f228).

37 June 2013 Research Reviews

Bodyweight and choice of antihypertensive

There have been reports of paradoxically in-creased cardiovascular event rates in people of normal bodyweight with cardiovascular

disease compared with overweight or obese patients with cardiovascular disease. It has also been reported that among patients with hypertension, obese patients have fewer cardiovascular events. Now, further pre-specified analysis of a previously reported trial has suggested that the protective effects of antihyperten-sive drugs may differ according to body weight.

In the ACCOMPLISH trial, treatment of hyperten-sion with an ACE inhibitor (benazepril) plus a calcium channel blocker (amlodipine) was compared with treatment with benazepril plus a diuretic (hydrochlorothia-zide). Of the 11,482 patients in the trial, 5,709 were obese (BMI 30 or greater), 4,157 were overweight (BMI 25 to <30), and 1,616 were of normal weight (BMI <25). The composite primary endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. After statistical adjustments, the primary endpoint rates (per 1,000 patient-years) were 30.7 (normal weight), 21.9 (overweight) and 18.2 (obese) in the benazepril plus hydrochlorothiazide group. Among obese patients, the event rates were similar in the two treatment groups, but among overweight and normal weight patients, event rates were significantly lower in the benazepril plus amlodipine group.

The researchers suggested that mechanisms of hypertension may differ between obese and normal weight patients. Whereas benazepril plus amlodipine was similarly effective in all bodyweight groups, benazepril plus hydrochlorothiazide was less effective in the lower BMI groups.

Weber MA et al. Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial. Lancet 2013; 381: 537–45; Messerli FH, Bangalore S. Diuretic-based regimens for obese patients? Ibid: 512-513 (comment).

38 June 2013 Research Reviews

Linoleic acid in diet and increased CV mortality

Polyunsaturated fatty acids (PUFAs) consist of various molecules of omega-6 (n-6) and omega-3 (n-3) PUFAs. Clinical benefits have been reported from some, but not

all, trials of the n-3 PUFAs, eicosapentaenoic acid and docosa-hexaenoic acid. There is little evidence, however, about the clini-cal effects of omega-6 linoleic acid (n-6 LA). In the Sydney Diet Heart Study (SDHS) of 1966–1973, replacing dietary saturated fatty acids (SFAs) with n-6-LA (from safflower oil) was found to be associated with increased overall mortality, but cardiovascular and coronary mortality rates were not reported. Now, data from the SDHS stored on magnetic tape have been recovered and re-analyzed.

A total of 458 men aged 30–59 years with a recent coronary event were randomized to either an intervention or a control group. The intervention group was asked to increase their n-6 LA intake so that PUFAs provided about 15 percent of energy intake (by using safflower oil and safflower oil margarine) and to reduce their intake of SFAs to <10 percent of energy intake and of cholesterol to <300 mg/day. The control group continued with their usual diets. All-cause mortality was 17.6 percent (intervention) versus 11.8 percent (controls), a significant 62 percent increase in the intervention group. Cardiovascular mortality was 17.2 percent versus 11.0 percent, and coronary disease mortality 16.3 percent versus 10.1 percent, with significant increases of 70 percent and 74 percent, respectively, in the intervention group compared with the control group. Adding these data to a previous meta-analysis gave nonsignificant increases of cardiovascular and coronary mortality rates after re-placing dietary SFAs with n-6 LA.

Increasing dietary n-6 LA while reducing dietary SFAs did not provide cardiovascular benefit and may have been harmful. An editorialist suggested that advice from the American Heart Association to maintain or increase n-6 LA should be reconsidered

Ramsden CE et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013;346 (Feb 9):12 (e8707); Calder PC. American Heart Association advice on omega 6 PUFAs cast into doubt. Ibid: 8 (f493).

39 June 2013 Research Reviews

Esophageal sphincter device

Up to 40 percent of patients with gastroesophageal reflux disease have incomplete relief from use of a proton pump inhibitor. Surgery in the form of Nis-

sen fundoplication may cause bloating, inability to belch or vomit, and dysphagia. Now, the effectiveness of a magnetic device to augment the esophageal sphincter has been as-sessed at 13 centers in the US and one in the Netherlands.

The device consists of a ring of magnetic beads connected by thin wires. It is placed around the lower esophagus lapa-roscopically so that it presses on the esophageal sphincter, augmenting the sphincter without compressing the muscle, so allowing the passage of food and also allowing belching or vomiting.

A total of 100 patients had the device implanted. The pri-mary outcome (normalization of esophageal acid exposure or at least 50 percent reduction in exposure at 1 year) was achieved in 64 patients. Ninety-three patients cut their use of proton pump inhibitors by at least a half, and quality of life improved in 92. Dysphagia occurred in 68 patients postop-eratively and persisted in 11 at 1 year and in four at 3 years. Six patients had serious adverse events, and the device was removed in all six.

The device was used successfully. Further studies are needed.

Ganz RA et al. Esophageal sphincter device for gastroesophageal reflux disease. NEJM 2013;368:719-727.

40 June 2013 Research Reviews

Fitness plus statins in dyslipidemia

Fitness resulting from exercise is associated with decreased cardiovas-cular risk, and statin treatment also reduces the risk in people with a high risk of cardiovascular disease. Now a study at two US Veterans

Affairs medical centers has shown that fitness and statin treatment provide greater protection than either alone.

The study included 10,043 men and women (mean age, 58.8 years; 97 percent men; mean BMI, 29.2 kg/m2) with dyslipidemia according to the In-ternational Classification of Diseases. They were classified into four levels of fitness based on peak metabolic equivalents (METs) achieved during an exercise tolerance test. Over an average follow-up of 10 years, mortality was 18.5 percent in subjects taking statins and 27.7 percent among those not tak-ing statins. Among subjects taking statins, those with a high level of fitness (>9 METs) had a 70 percent reduction in mortality compared with those with a low level of fitness (5 METs or less). Fitness was also associated with re-duced mortality among people not taking statins, but the effect of fitness was greater among those taking statins.

Fitness and statin treatment are independently associated with reduced mortality. The two combined lower the risk further.

Kokkinos PF et al. Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: a cohort study Lancet 2013;381(9864):394-9.

Vitamins and antioxidants to prevent cardiovascular disease: Not effective

It has been suggested that vitamin and antioxidant dietary supplements might help to prevent cardiovas-cular disease. A systematic review and meta-analysis has provided no support to the suggestion.

The analysis included 50 randomized controlled trials (294,478 participants). Taking vitamins and an-tioxidants did not affect the risk of cardiovascular disease (relative risk, 1.0; 95 percent CI, 0.98–1.02). Exten-sive subgroup meta-analyses did not reveal any group of patients or type of supplement that had a significant beneficial effect.

Vitamin and antioxidant supplements do not reduce the risk of cardiovascular disease.

Myung S-K et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ 2013;346:12(f10).

41 June 2013 Research Reviews

Antidepressants and prolonged QTc

The US Food and Drug Administration has warned about a prolongation of corrected QT interval (QTc) with use of

the antidepressant citalopram. Prolonged QTc is associated with increased risk of ventricular arrhythmias. Now, a study in a large healthcare system in the US has confirmed prolongation of QTc with citalopram, escitalopram, and amitrip-tyline.

The study included 38,397 patients who had an ECG after being prescribed an anti-depressant or methadone between February 1990 and August 2011. The antidepressants studied were the selective serotonin reup-take inhibitors (SSRIs) citalopram, escitalopram, fluoxetine, paroxetine, and sertraline, and non-SSRI anti-depressants amitriptyline, nortriptyline, bupropion, duloxetine, mirtazapine, and venlafaxine. The opi-oid methadone was included to confirm assay sensitivity since it is known to prolong QTc. There were significant dose-related associations between citalopram, escitalopram and amitriptyline and prolonged QTc, and between bupropion and shortened QTc. None of the other seven antidepressants had a significant effect on QTc.

Prolonged QTc was associated with use of citalopram, escitalopram and amitriptyline. The risk is greater with older and more ill patients.

Castro VM et al. QT interval and antidepressant use: a cross sectional study of health records. BMJ 2013; 346 (Feb 9):15(f288).

42 June 2013 CalendarJUNE23rd Conference of the Asian Pacific Association for the Study of the Liver6/6/2013 to 9/6/2013Location: SingaporeInfo: APASL SecretariatEmail: apaslconference@kenes.comWebsite: www.apaslconference.org

International Digestive Disease Forum 20138/6/2013 to 9/6/2013Location: Hong KongInfo: UBM Medica Pacific LimitedTel: (852) 2155 8557 Fax: (852) 2559 6910Email: info@iddforum.comWebsite: www.iddforum.com

3rd World Congress of Thoracic Imaging8/6/2013 to 11/6/2013Location: Seoul, KoreaInfo: WCTI SecretariatTel: (82) 2 3452 7245/(82) 2 3471 8555Fax: (82) 2 521 8683Email: wcti2013@insession.co.kr Website: www.wcti2013.org

International Liver Transplantation Society (ILTS) 19th Annual International Congress12/6/2013 to 15/6/2013Location: Sydney, AustraliaInfo: ILTS Tel: (856) 439 0500Fax: (856) 439 0525Email: ilts@ilts.org Website: http://2013.ilts.org

European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology12/6/2013 to 15/6/2013Location: Madrid, SpainInfo: EULAR SecretariatTel: (41) 22 339 95 90Fax: (41) 22 339 96 01Email: eular2013@mci-group.com Website: www.eular.org

17th International Congress of Parkinson’s Disease and Movement Disorders16/6/2013 to 20/6/2013Location: Sydney, AustraliaInfo: MDS Congress StaffTel: (1) 414 276 2145Fax: (1) 414 276 3349Email: congress@movementdisorders.org Website: www.mdscongress2013.org

12th Asian and Oceanic Society of Regional Anaesthesia and Pain Medicine Congress 19/6/2013 to 22/6/2013Location: Kuching, Sarawak, MalaysiaInfo: AOSRA-PM 2013 Congress SecretariatTel: (603) 4023 4700, 4025 4700, 4025 3700Fax: (603) 4023 8100Email: secretariat@aosra2013.org Website: http://www.aosra2013.org/

American Diabetes Association 73rd Scientific Sessions 21/6/213 to 25/6/2013Location: Chicago, Illinois, USInfo: ADA Registration Customer Care CenterTel: (1) 415 268 2086Email: ADAReg@cmrus.comWebsite: http://scientificsessions.diabetes.org

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention30/6/2013 to 3/7/2013Location: Kuala Lumpur, MalaysiaInfo: IASTel: (41) 61 560 75 35Fax: (41) 61 686 77 88Email: info@ias2013.orgWebsite: www.ias2013.org

JULy9th Asian Dermatological Congress10/7/2013 to 13/7/2013Location: Hong KongInfo: ADC 2013 SecretariatTel: (852) 3151 8900Email: adc2013@swiretravel.com Website: www.adc2013.org

43 June 2013 CalendarUPCOMINg13th Asian Federation of Sports Medicine Congress25/9/2013 to 28/9/2013Location: Kuala Lumpur, MalaysiaInfo: AFSM OrganizersEmail: 13afsm@gmail.comWebsite: www.13afsm.com

European Cancer Congress 2013 (ECCO-ESMO-ESTRO) 27/9/2013 to 1/10/2013Location: Amsterdam, NetherlandsInfo: ECCO SecretariatTel: (32) 2 775 02 01Fax: (32) 2 775 02 00Email: ecco@ecco-org.eu Website: http://eccamsterdam2013.ecco-org.eu/

Taiwan Digestive Disease Week 20134/10/2013 to 6/10/2013Location: Taipei, TaiwanInfo: Congress SecretariatEmail: service@tddw.org Website: www.tddw.org

13th International Workshop on Cardiac Arrhythmias - VeniceArrhythmias 201327/10/2013 to 29/10/2013Location: Venice, ItalyInfo: VeniceArrhythmias 2013 Organizing SecretariatTel: (39) 0541 305830Fax: (39) 0541 305842Email: info@venicearrhythmias.orgWebsite: www.venicearrhythmias.org

44 June 2013 After Hours

The locals will tell you that the real Golden Bay only begins once you have crossed over “the hills” that separate

Motueka from Upper Takaka – where upon you enter an area that has been dubbed “the safest place on Earth” (incidentally also one of the most isolated areas in New Zealand). For should the only “mountain road” that connects the bay with the rest of the country be cut off (by a landslide, the like of which happen very often here), then the area would be completely cut off from civilization.

Interestingly, a German television station’s prodigal claim in the late 1980’s (when half of that country was worrying about a potential nuclear apocalypse after the Chernobyl reac-tor melt-downs), that the area in “the north-western most point of the South Island of

New Zealand” was sufficiently isolated to withstand fall-out or radiation flow from any nuclear catastrophe or war, led to many Ger-mans emigrating to the region throughout the 80’s and early 90’s. So much so that Germans now make up 10 percent of the total popula-tion of Golden Bay.

So it is a special area. Many people believe that the bay is named after the beaches; that when viewed at a certain angle to the sun, juxtaposed to the crystal clear emerald blue waters, appear eerily (or perhaps beautifully so) “golden” in hue.

The more esoteric locals (or even scientifi-cally or mathematically savvy) swear that the region adopted its name due to the presence of the natural spiral that forms when you fol-low the trajectory of Onetahua (or “Farewell

Christopher von Roy seeks out one of New Zealand’s most alluring and remote places – Golden Bay

All Things

GoldenOnetahua (Farewell Spit)

Photo courtesy of Christopher von Roy

45 June 2013 After HoursSpit”), the natural sand mass that extends 35 KM due north-east from Puponga (about 40 KM from Takaka – the beginning of Golden Bay), on the north-eastern most point of the South Island of New Zealand. When extend-ed this sand spit would follow the natural curvature of a Fibonacci spiral (golden spi-ral) – where the extent of the curl of the spiral obeys the “golden ratio” or phi – 1.6180, pub-lished by the Italian mathematician Nicolo Fi-bonacci in 1202. Whilst adding up ascending numbers continuously (1 + 1 + 2 + 3 + 5 + 8 + 13 + 21) Fibonacci found that if you took out any of the sums and divided it by its previous sum, the answer would always be a constant ratio, yes, 1.6180 – the golden ratio.

If you start at Rata beach (just 20 minutes from the illustrious Abel Tasman National Park) and follow the coast along up until Farewell Spit and extend it, you would get the perfect spiral pattern (as observed in most of nature; the ellipsis pattern on a Nautilus shell, the shape of the Milky Way, the way a tree grows its branches – when viewed from above).

This slightly esoteric interpretation of the name of this region is reflective of the ambi-ence (general feeling) you get once you’ve had time to soak up and appreciate the whole area altogether. In some parts it feels as though time has stopped, some time in the 60’s (the 1960’s that is, though in some places, the 1860’s would also be apt – ie, some places have no running water, no electricity, no in-ternet, no telephone etc.)

It’s difficult to capture in words exactly the impact this area has on a person, but it is magical, for want of a better adjective. After driving through Takaka (the main “metro-pole” or cultural center of Golden Bay) you come upon a multitude of little “townships”

all the while enjoying the bay on one side and the white capped mountains on the other. The biggest of these townships, Collingwood, can boast that it almost became New Zealand’s capital back in the 1800’s when large coal and gold reserves were discovered in a nearby re-gion. Collingwood also serves as a base for “eco” bus tours that drive tourists up on to the “spit” and even right to the end of it. To drive to the end of the 36 KM land spit from Collingwood takes about 6 hours Incidentally this is the only way to get to the end of the spit as the Department of Conservation (DOC) has deemed only 4 KM as “walkable” – and then there are all sorts of reasons (some even mysterious) as to why this is (the most haunt-ing of which would be quick sand. One local had even informed me that they had “lost” several tourists due to shifting sands on the spit. I wasn’t quite sure if I should believe him or not.

The region is also home to one of the largest bird sanctuaries in the southern hemisphere, extending from the tip of the spit all the way down to the bottom the Kahurangi National Forest south. This forest extends 150 KM in longitude and 200 KM in latitude – making it the largest forest in New Zealand. The forest is home to the legendary “Heaphy track” – an 84 KM hike through the national park. This is a walk that can take up to 5 days for more dis-cerning hikers (or those who like to take their time soaking in the endemic flora and fauna). But experienced hikers can complete the track in 3 days (walking at a medium to fast pace). There are five DOC huts throughout the walk.

There are also plenty of other shorter hikes in the region which can also allow you to get a great feel for the expansiveness of both the forest and the mighty, untamed Wharariki beach to the west.

46 June 2013 After HoursThe best day hike would have to be the

Hilltop Hike (from Puponga Farm to Whara-riki beach) – a 4-5 hour round–walk that takes the walker from the sheep farms below at the base of Farewell Spit, through the hilltop hike over the famous “Old Man” rock boulders – that stand some 150 meters from the ground below and the hikers have to traverse. The walk takes you all the way to Wharariki beach and the seal colonies there – make sure you walk past the islands when you enter Whara-riki beach; this will give you the best view of the incredible Archway Islands.

Lastly, the whole region has a very im-portant place in Maori culture and folklore. It is a gateway for departing souls, much like Cape Reinga on the tip of the North Is-land of New Zealand. All of the Kahurangi National Park is deemed “tapu” or sacred in Maori culture. This stems from the his-tory of the region and the fierce battles that were fought here between Maori tribes from both the North and South Islands com-peting for access to the one of the largest pounamu (jade/greenstone) mines in the country.

For more information about Golden Bay and its surrounds:www.goldenbay.co.nz, www.farewellspit.com, www.doc.govt.nz/parks-and-recreation/tracks.../heaphy-track

47 June 2013 Humor

“With all due respect Dr. Chelm, you are not doing it right!”

“How can I help you?”

“Not you again!”

“Calm down Mrs. Balboa. About those butterflies in

your stomach, are you sure you didn’t sleep with your

mouth open?

“Cancel all appointments!”

“So, you forget things, therefore you think you have Alzheimer’s. Can you give me an example of

something you forgot?”

“Artery problems? I suppose that explains why I’m not good

at drawing!”

Publisher : Ben Yeo

Managing Editor : Greg Town

Senior Editor : Christina Lau

Contributing Editors : Jacky Suen (Hong Kong), Saras Ramiya, Leonard Yap, Pank Jit Sin, Malvinderjit Kaur Dhillon (Malaysia), Yves St. James Aquino, M.D. (Philippines), Radha Chitale, Elvira Manzano, Rajesh Kumar, Grace Ling (Singapore)

Publication Manager : Marisa Lam

Designers : Razli Rahman, Charity Chan, Lisa Low, Joseph Nacpil, Agnes Chieng, Sam Shum, Cindy Ang, Sharen Lee

Production : Edwin Yu, Ho Wai Hung, Jasmine Chay

Circulation Executive : Christine Chok

Accounting Manager : Minty Kwan

Advertising Co-ordinator : Rachael Tan

Published by : MIMS Pte Ltd 27th Floor, OTB Building, 160 Gloucester Road, Wanchai, Hong Kong Tel: (852) 2559 5888 Fax: (852) 2559 6910 Email: enquiry@medicaltribune.com

Advertising Enquiries:

China : Yang Xuan Tel: (8621) 6157 3888 Email: enquiry.cn@mims.com

Hong Kong : Kristina Lo-Kurtz, Miranda Wong, Marisa Lam, Jacqueline Cheung Tel: (852) 2559 5888 Email: enquiry.hk@mims.com

India : Monica Bhatia Tel: (9180) 2349 4644 Email: enquiry.in@mims.com

Korea : Choe Eun Young Tel: (822) 3019 9350 Email: inquiry@kimsonline.co.kr

Malaysia : Sheena Subash, Lee Pek Lian, Sumitra Pakry, Grace Yeoh Tel: (603) 7954 2910 Email: enquiry.my@mims.com

Philippines : Marian Chua, Kim Pagsuyuin, Rowena Belgica, Philip Katipunan Tel: (632) 886 0333 Email: enquiry.ph@mims.com

Singapore : Jason Bernstein, Carrie Ong, Josephine Cheong, Melanie Nyam Tel: (65) 6290 7400 Email: enquiry.sg@mims.com

Thailand : Wipa Sriwijitchok Tel: (662) 741 5354 Email: enquiry.th@mims.com

Vietnam : Nguyen Thi Lan Huong, Nguyen Thi My Dung Tel: (848) 3829 7923 Email: enquiry.vn@mims.com

Europe/USA : Kristina Lo-Kurtz Tel: (852) 2116 4352 Email: kristina.lokurtz@mims.com

Medical Tribune is published 12 times a year (23 times in Malaysia) by MIMS Pte Ltd. Medical Tribune is on controlled circulation publication to medical practitioners in Asia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of MIMS Pte Ltd. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions.

© 2013 MIMS Pte Ltd. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. MIMS Pte Ltd does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature.

Philippine edition: Entered as second class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by KHL Printing Co Pte Ltd, 57 Loyang Drive, Singapore 508968.

ISSN 1608-5086