May 2013

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Diabetes research failing to address prevention

CONFERENCE HPS2-THRIVE trial: Negative results for niacin

NEWS Low melatonin secretion linked to diabetes risk

IN PRACTICE Managing wrist pain

AFTER HOURS Getting around on the London Underground

May 2013

Diabetes research failing to address prevention

Laura Dobberstein

he prevention of diabetes is being overlooked by diabetes researchers, according to a recent study. Our descriptive analysis found that the majority of registered [diabetes] trials involve drug therapies rather than preventative or non-drug interventions, said study author Dr. Jennifer Green of Duke University Medical Center in Durham, North Carolina, US, and colleagues. Green and her team examined 2,484 interventional diabetes trials registered on the ClinicalTrials.gov website between 2007 and 2010, to better understand which aspects of the disease were being addressed. [Diabetologia 2013; doi:10.1007/s00125-013-2890-4] While 75 percent of the trials had a primarily therapeutic purpose, only 10 percent focused on prevention. Sixty-three percent of interventions used drugs and only 12 percent looked at modifiable behaviors. Their findings also indicated some important demographic disparities of trials, which tended to exclude children and the elderly, were often small in size and duration, did not geographically represent populations of those living with diabetes, and did not focus on significant cardiovascular outcomes like heart attack and stroke. Twenty percent of adults over age 65 have diabetes, but less than 1 percent of the trials included patients in this age group. Most trials excluded patients over 75 years of age and 30.8 percent excluded those over the age of 65. Four percent of trials targeted those under the age of 18. This low number of pedi-

atric trials may accurately reflect the proportion of people in this age group affected by diabetes. However, arguments exist as to why this group should be better represented in research. A 3 percent annual increase in type 1 diabetes currently exists among those under the age of 18. In addition, children have a higher chance of developing complications during their disease course and benefit more from better disease management than their older counterparts. The small size and duration of the trials concerned the researchers. The average length of a trial was less than 2 years. Over half of all trials had fewer than 100 participants and 91 percent had fewer than 500 participants. Complications like diabetic retinopathy, lower extremity amputation and end-stage renal disease vary among ethnic groups, making it important to include a diverse background of people in diabetes research. Study populations were overrepresented by patients from North America, Western Europe and certain Asian countries, but underrepresented by patients from other important regions such as Russia, Brazil and the Middle East. Cardiovascular complications related to diabetes have become an important research topic, particularly in relation to medication development. Yet mortality and cardiovascular complications were only reported in 1.4 percent of trials. The researchers concluded that current clinical trials on diabetes research do not adequately address disease prevention, management or therapeutic safety. The results from this study build a better understanding of ongoing research and could help direct future research activities and resources.

May 2013

Fast foods going cardio smart

Naomi Rodrig
ublic education efforts promoting healthy lifestyle for the prevention of cardiovascular disease seem to be bearing fruit as some fast food chains are moving towards healthier menu options. At the recent American College of Cardiology (ACC) Annual Scientific Sessions in San Francisco, California, US, Subway was promoting heart-healthy meals, with detailed nutritional information about its sandwich and beverage choices. Subway was the first fast food chain to receive the American Heart Associations (AHA) Heart Check certification by meeting AHAs criteria. Heart Check meals contain <700 calories; <30 percent of calories from fat; low sodium, saturated fat and cholesterol; and at least 10 percent of daily value of beneficial nutrients such as fiber from fruits and vegetables, plus vitamins. Lowering salt content is a particular focus for Subway. Having reduced the sodium content by 15 percent across our product line, we are continuing to look for new ways to reduce sodium while we relentlessly pursue an improved overall nutritional profile for every meal we serve, the company spokesman announced recently. Furthermore, Subways kids meals now have <5 percent of calories from added sugar. Targeting health education to the younger generation is the most effective way for future population health, said past ACC president, Dr. Valentin Fuster, in his opening keynote lecture. Focusing on disease prevention efforts, Fuster pioneered health education programs in elementary schools in Spain and

Brazil, which showed that children aged 4-6 years are the most likely to adopt healthy diet and lifestyle in the years ahead. Coca Cola, synonymous with sugary drinks, has also diversified in the past few years to produce a wide range of healthy beverages, including natural juices, and protein-rich or vitamin-fortified drinks. Marketed under different brand names, some of these drinks have gained popularity among health-conscious consumers, but are still far from replacing the traditional coke. Further, ACC delegates who sampled the new drinks at Coca Colas booth remarked that most of them are still too sweet. In addition, Coca Cola has partnered with the US National Heart, Lung and Blood Institute in supporting The Heart Truth campaign a program that aims to educate people and raise awareness about heart health and provide tools and resources for heart-healthy lifestyle. Doing good for the public also makes good business sense for the food chains as consumers get more knowledgeable and conscious about their diet, demanding healthier food choices, including in fast food outlets.

May 2013

Forum

Conquering cardiovascular disease around the globe

Excerpted from a keynote lecture by Dr. William Zoghbi, president of the American College of Cardiology (ACC), during the 62nd Annual Scientific Sessions of the ACC, held recently in San Francisco, California, US. hen we think about overall cardiovascular care, we need to consider all the elements. Certainly, first and foremost is the care of the patient with heart disease. Of course there are many other factors that we must consider and dedicate our efforts to, starting with early detection of disease, raising awareness about the impact of obesity, inculcating healthy behaviors and considering the contributions of genetic factors and, importantly, ethnic backgrounds. We aim for better care, better population health and affordable care from the perspective of both the patient and society. The ACCs answer to achieving this triple aim has emphasized quality, value and professionalism. The college has also focused on patient-centered care and is seeking collaborations among organizations for the development of guidelines, quality tools and health policies. Key ACC initiatives to help advance cardiovascular health include data registries and their impact, appropriate use of diagnostic modalities and interventions, strategies to empower patients with knowledge, and approaches to deal with public health challenges, both locally and globally. National data registries provide important data on practice of medicine and patient outcomes. The ACCs National Cardiovascular

Data Registry, or NCDR, celebrates its 15th year this year and it has become the flagship of registries, growing to a total of seven registries. These cover most areas of cardiology, including interventional cardiology, implantable cardioverter defibrillator therapy, management of acute myocardial infarction, congenital heart disease and, most recently, transcatheter valve therapy. These continually enrolling registries have more than 24 million records.

May 2013

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research, medications, devices and catheterbased and surgical interventions. However, many challenges remain. In the US, many patients who need to take aspirin are not. And many are in need of better blood pressure control and cholesterol management. Smoking rates, although better than in other countries, are still far from optimal. Even more urgent are challenges looming globally. Death from cardiovascular disease exceeds that from any other disease and accounts for about one-third of total deaths worldwide. It is higher than cancer, respiratory disease and diabetes, the other main noncommunicable diseases (NCDs), combined. The projected trends are alarming as they gradually increase for both cardiovascular disease and cancer. There are 10 highest risk factors for cause of total death worldwide. The most important is high blood pressure followed by tobacco use, high glucose, physical inactivity, overweight and obesity, and high cholesterol. Many of these risk factors are the same for other NCDs. Therefore, addressing them will have a major impact on global health, not only cardiovascular health. Prompted by the NCD Alliance, the United Nations had its first ever high-level meeting on NCDs in September 2011. The outcome of the summit was a political declaration that called on the World Health Organization to establish global targets for curbing NCDs. Indeed, the World Health Assembly met in Geneva in May 2012 and approved a monumental goal: a 25 percent reduction in premature mortality from NCDs by the year 2025. To achieve that overall goal, the following targets were adopted: reductions in tobacco smoking, physical inactivity, excessive alcohol use, salt intake, raised blood pressure,

What is also exciting is that some of these registries have gone global, with presence in Asia, the Middle East and South America. This enables sharing and comparing of cardiovascular care quality between nations worldwide with the goal of improving cardiovascular care. Our most recent partnership with the Society for Thoracic Surgery, as well as regulatory agencies, payers and industry, ushers in a new registry paradigm this one for patients with advanced aortic stenosis mandating participation for reimbursement while monitoring quality, patient outcome and supporting research and innovation. The power of data reporting can change clinical practice and improve quality of care. Before reporting door-to-balloon data for treatment of acute heart attack, most hospitals and physicians believed they were doing a great job in this type of care. With the data, the percent of patients achieving a doorto-balloon time of less than 90 minutes improved. Such data also lowered the rate of inappropriate angioplasties in favor of medical treatment. Reflecting on the application of knowledge, while science tells us what we can do, guidelines tell us what we should do, and registries show us what we are actually doing and will likely be doing in the future. A key component of high-quality care places an emphasis on the patient. This is where we need to be spreading the word about healthy living and healthy choices in the community. On one hand, looking back on the impact of cardiovascular interventions and outcomes, it is really gratifying to see the significant decline in cardiovascular mortality in the US over the past 40 years, thanks to advances in

May 2013

Forum
funding for the NCD movement currently NCDs cause about 60 percent of global deaths yet receive about one percent of health funding. So the time is now for us to act and work collaboratively. Cardiovascular disease is a global problem. We can protect population health by taking a global perspective and working together with ACC chapters and national and international organizations to reach this noble goal.

diabetes and obesity. Availability of essential medications to prevent heart attack and stroke was also emphasized. Going forward, there are challenges but great opportunities to reach this ultimate goal. As risk factors are so prevalent and traditional treatments are affordable, there is no need for new inventions globally. A big challenge is implementing the resolutions of various targets, knowing these may vary by nation. It is crucial to establish better

May 2013

Conference Coverage

62nd Annual Scientific Sessions of the American College of Cardiology, 9-11 March, San Francisco, California, US

Preventing cardiovascular disease: Do the very elderly require a different approach?

Excerpted from a lecture by Dr. Janice Schwartz, clinical professor of Medicine, Bioengineering, and Therapeutic Science at the University of California, San Francisco, US, during the 62nd Annual Scientific Sessions of the American College of Cardiology, held recently in San Francisco, California, US. hen I first thought about whether the very elderly require a different treatment approach, I said yes. Its obvious, there is no question we should be treating elderly patients differently than younger patients. I think the individual treatment goals might differ as you have older patients. They certainly have more comorbidities and those are going to influence our choices and limit our options. And clearly cost limits the options elderly women in the US have the highest level of poverty of any group. But if the goal is the best therapy for each patient, then we have the same goal for all patients. However, maybe the approach should be to choose options and therapy that benefit the patient in their life span. Im going to define benefit as meeting the goals of the patient and improving the function or quality of life that is a wonderful goal and cardiologists are coming around to that. We no longer look at just prolongation of life as a good outcome, were willing to say fewer hospitalizations and decreases of morbidity are a valid goal. Im also going to introduce the concept that we would like to prevent decline in de-

Regular activity in the very elderly improves quality of life and life expectancy.

pendency. If you ask your patients and give them informed consent before procedures, they might tell you they dont mind dying but

May 2013

Conference Coverage
In an average life span for people between 70-90 years, there is considerable variability. So I think we have to do a better job when we come to individual decisions about our patients to try and project their life span. Traditional risk calculators such as the Framingham risk score and the Reynolds risk score do not help decision making for the elderly. Risk factors that are important in the older group are age, sex, body mass index, the presence of chronic diseases, smoking, difficulty with the activities of daily living, managing finances, the ability to walk several blocks, and trouble pushing large objects. Prognosis calculators that weigh these indicators for the elderly might show that the odds of dying within 4 years for someone who does not have diabetes or is overweight and doesnt have cancer or smoke but has difficulty bathing or with other activities of daily living might be 59 percent. However, the addition of congestive heart failure to a person with this profile would only increase the odds of dying within 4 years to 64 percent. The things that drive life expectancy in this group are really the activities of daily living bathing, dressing, managing finances, and so on certainly much more so than heart failure. Similar risk calculators for this group include determining whether patients have been hospitalized, if they can read a newspaper, do they have hearing impairment or weight loss, are they receiving home care services and whether they are poor. So if the risk factors are different, should treatment be different? Treat with life span in mind As an example, one trial compared statin therapy with placebo in 5,804 patients aged

they dont want to wake up with a stroke and be dependent. Consider life expectancy over patient age When we think about diseases and risk factors, we really have a goal of treatment, and we can do it in the middle-aged and younger patients. The goal is prolonging their life. But as people get older, the things that become important are quality of life and maintenance of function. The challenge is, of course, when were going to start shifting from thinking about life prolongation to quality of life and function. The key concepts that provide a framework for decision making are to estimate life expectancy in the elderly and very elderly, recognize the importance of function and the lagtime until benefit or harm of therapies, and patient-centered decisions. Data from the US Census Bureau show that an 85-year-old man might have on average 5.7 years to live, a 90-year-old has another 4 years to live and if you make it to 100 you will probably live another 2 years, on average. For women those years are even longer. The 85-year-old might be living out to about 7 years, the 90-year-old has another five years and the 100-year-old is going to have about 2.3 years.

The challenge is, of course, when were going to start shifting to quality of life and function

from thinking about life prolongation

But thats average life span and, as the economist Milton Friedman said: Never try to walk across a river just because it has an average depth of four feet.

May 2013

Conference Coverage
Make exercise a priority The one thing that helps everything a patient has is exercise. We should be the leaders in developing exercise programs that are going to benefit the whole patient, especially the older patient. It doesnt need to be intense exercise like it should be for cardiovascular benefit in middle-aged men. There are no shortterm adverse effects, there is a short lag-time for benefit and the benefits hit the body both above and below the waist. The US National Institutes of Health says regular activity improves quality of life, extends life and decreases the risk of cardiovascular disease and other illnesses and disabilities. To conclude, they key considerations for the very elderly are estimated life expectancy not age alone lag-time to potential benefit and adverse treatment effects and burden. Estimates of benefits and harms should be weighted with qualitative judgments of individuals values and preferences. Function and not cardiovascular risk factors have the greatest impact on life expectancy and quality of life in the very old. And we must focus on improving function with exercise and preventing the conditions that decrease function and quality of life.

70-82 years over 4 years with a history or risk of vascular disease. [Lancet 2002;360:16231630] Even by the time one begins to see benefits from the statin, the risk of death or cardiovascular events remains almost the same, and certainly up to 2 years. So I would say someone with a life expectancy less than 2 years is not going to benefit and therapy may well hurt them, it will certainly cost more. If we also look at the evidence for aspirin for primary prevention, we see aspirin reduces the risk of myocardial ischemic events, with a higher rate of bleeding, according to one study, and does not prolong life. Again, the treated time-to-benefit is not until 3.7-10 years out. [Lancet 2009;373:1849-1860] Here patients may not live that long so they dont get the potential benefit, there is no difference in cardiovascular mortality but bleeds happen earlier and they risk hemorrhagic stroke. The American Geriatric Society says yes, the elderly require different approaches, for example, when picking medications for hypertension, using aspirin for primary prevention of cardiac events, using potentially inappropriate drugs with caution and advise against tight glucose control, calling moderate control better.

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May 2013

Conference Coverage

62nd Annual Scientific Sessions of the American College of Cardiology, 9-11 March, San Francisco, California, US

Cangrelor outperforms clopidogrel during PCI

Elvira Manzano
he new anti-clotting agent cangrelor, given during percutaneous coronary intervention (PCI), performed better than mainstay drug clopidogrel at reducing ischemic events, according to results from the CHAMPION PHOENIX* trial. Cangrelor significantly reduced the primary endpoint of composite rate of death, myocardial infarction (MI), ischemia-driven revascularization and stent thrombosis by 22 percent at 48 hours post-randomization (p=0.005) without an increased risk of severe bleeding (p=0.44). This benefit was driven by a 20 percent reduction in the rate of acute MI and a 38 percent reduction in the incidence of stent thrombosis. [N Engl J Med 2013; doi:10.1056/NEJMoa1300815] Cangrelor may be an attractive option across the full spectrum of patients undergoing PCI, said first study author Dr. Deepak L. Bhatt from the VA Boston Healthcare System and Brigham and Womens Hospital in Boston, Massachusetts, US. Unlike clopidogrel, cangrelor takes effect rapidly and wears off within an hour of infusion, which allows for flexibility to initiate and stop ADP inhibition immediately in patients requiring urgent surgery or in those who develop bleeding complications, Bhatt added. Despite being a more potent antithrombotic than the comparator, there was no bad bleeding that would be worrisome when add-

Cangrelor successfully reduced ischemic events without increased risk of severe bleeding, but it wont be routine therapy for all PCI patients yet.

ing another drug into the medical regimen, said Dr. Robert Harrington of Stanford University School of Medicine in California, US, and co-principal investigator of CHAMPION PHOENIX. CHAMPION PHOENIX is a randomized, double-blind, all-comer trial involving 11,145 patients with acute coronary syndrome (stable angina, non-STEMI or STEMI) or other conditions requiring urgent or elective PCI, randomized to a bolus and infusion of cangrelor or a loading dose of oral clopidogrel (600 mg or 300 mg). Overall, procedural complications were less common with cangrelor (3.4 percent vs 4.5 percent; p=0.002) as well as the need for rescue therapy with glycoprotein IIb/IIIa in-

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Conference Coverage
In an accompanying editorial, Drs. Richard A. Lange and L. David Hillis, both from the University of Texas Health Sciences Center at San Antonio, Texas, US, noted that more than a third of patients in the study received 300 mg of clopidogrel, which is inferior to the 600mg dose in achieving platelet inhibition and preventing periprocedural ischemic events. Given such concerns, the routine use of this therapy for all patients undergoing PCI is not yet justified, they said. [N Engl J Med 2013; doi:10.1056/NEJMe1302504]
*  CHAMPION PHOENIX: A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention **  BRIDGE: Maintenance of Platelet Inhibition With Cangrelor

hibitors (p<0.001). The incidence of stent thrombosis at 48 hours, the secondary endpoint, was also less frequent with cangrelor (0.8 percent vs 1.4 percent; p=0.01). Moreover, the benefit in the composite efficacy endpoint was sustained in the cangrelor arm at 30 days of follow-up (p=0.01). Based on these results and the previous BRIDGE** trial, cangrelors manufacturer is planning to file an approval with the US Food and Drug Administration. Intravenous cangrelor appears to be a better strategy than oral clopidogrel for ADP blockade during PCI. Whether or not it is better than other ADP-receptor blockers, such as prasugrel or ticagrelor which are currently in use, remains to be studied, Harrington concluded.

HPS2-THRIVE trial: Negative results for niacin

Radha Chitale

esults from the HPS2-THRIVE* trial, the largest study of extended-release (ER) niacin plus the anti-flushing agent, laropiprant, in high-risk heart patients showed that the drug failed to reduce the risk of major vascular events compared with statin therapy and caused a significant number of serious adverse events in the study population, which experts said confirmed the end of the drugs clinical value. This was a disappointing result but nevertheless is a clear and reliable result, said lead author Professor Jane Armitage of the Univer-

HPS2-THRIVE takes niacin-based therapy off the table.

sity of Oxford in the UK. In the light of these findings we consider that the role of ER niacin preparations for the prevention of cardiovascular disease needs to be reconsidered.

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Conference Coverage
academic affairs at St. Josephs Health System in Atlanta, Georgia, US, noted that, despite niacins poor showing in this and other trials, it is typically used in patients with higher, less well-controlled LDL cholesterol levels and patients with metabolic syndrome, which the current trial does not account for. Armitage said the trial did show a trend toward greater benefit for patients entering the trial with higher LDL cholesterol, but the absolute benefit in these patients was still small compared with the amount of adverse events. We were not able to identify any particular group of patients who we felt any benefits from the reduction in major vascular events would be outweighed by these adverse effects on a variety of other systems, she said. The HPS2-THRIVE results are not entirely surprising given the poor results of niacin in previous trials, notably the AIM-HIGH** trial in 2011, which was halted more than a year earlier than planned when it failed to reduce the risk of cardiovascular events and increased risk of ischemic stroke. [N Engl J Med 2011;365:2255-2267] Merck Sharp & Dohme Ltd (MSD) suspended global sales of their niacin/laropiprant product, Tredaptive, in January 2013. It is unclear whether any therapy involving lipid manipulation, particularly raising HDL levels, could be cardioprotective, but Armitage indicated that the case for niacin appears to be closed.
* HPS2-THRIVE: Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events ** AIM-HIGH: Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes

HPS2-THRIVE randomized 25,673 highrisk heart patients from Europe and China to a combination of ER niacin/laropiprant or a placebo. All patients received standard lowdensity lipoprotein (LDL) lowering therapy consisting of simvastatin with or without ezetimibe. The most striking aspect of the trial was the excess of serious adverse events as a result of niacin therapyevents significant enough to result in hospitalization or significant illness, which went beyond the well- known side effects of niacin. Over the course of the 3.9-year study, there were 31 serious adverse events per 1,000 niacin-treated patients. Compared with placebo, niacin resulted in an excess of 3.7 percent diabetic complications, 1.8 percent new-onset diabetes, 1.4 percent infections, and 1 percent gastrointestinal adverse events (p<0.0001 for all). The researchers also reported an excess of 0.7 percent musculoskeletal (p=0.0008), 0.04 percent heart failure (p=0.05), 0.7 percent bleeding in the gut and intracranially (p=0.0002), and 0.3 percent dermatological (p=0.0026) serious adverse events. There was no difference in efficacy between niacin- and placebo-treated patients, as demonstrated by a similar number of major vascular events, including non-fatal myocardial infarction, coronary death, any stroke, or revascularization (13.2 percent vs 13.7 percent; p=0.29). Niacin did cause an average LDL reduction of 10 mg/dL, triglyceride reduction of 33 mg/ dL and high-density lipoprotein (HDL) increase of 6 mg/dL. However, the 10-15 percent benefit that Armitage said should have resulted from these lipid changes was not observed. Discussant Dr. Spencer King, director of

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May 2013

Conference Coverage

62nd Annual Scientific Sessions of the American College of Cardiology, 9-11 March, San Francisco, California, US

Long-term outcomes of TAVR, surgery similar in severe aortic stenosis

Elvira Manzano

ranscatheter aortic valve replacement (TAVR) remains comparable to open heart surgery in the long term in patients with severe aortic stenosis at high risk for surgery, according to the updated results of the PARTNER* trial, but mortality rates with both approaches are high. At 3 years, there was no statistical difference in the primary endpoint of all-cause mortality between the two groups 44.2 percent with TAVR and 44.8 percent with open heart surgery. Stroke rates were also no different at 8.2 percent and 9.3 percent, respectively. Paravalvular leaks or regurgitation were persistent and fatal. TAVR should be considered an alternative to surgery with similar mortality and other major clinical outcomes, said study presenter Dr. Vinod Thourani from Emory University School of Medicine in Atlanta, Georgia, US. Future efforts should be directed toward reducing TAVR-procedure-related complications, including strokes, vascular events and paravalvular regurgitation. One-year results from the PARTNER A trial, presented 2 years ago, showed similar mortality outcomes for TAVR and surgery. However, strokes and transient ischemic attacks (TIA) were significantly higher with TAVR. The trial was extended to assess longterm outcomes and valve performance. At 2 years, even mild paravalvular regurgitation was associated with increased mortality. PARTNER A included 699 patients (median age, 84.1) enrolled between May 2007 and

September 2009 and randomized to catheterbased procedure either through transapical or transfemoral access or surgery. At 3 years, there were more major vascular complications with TAVR (12.5 percent vs 3.8 percent; p<0.001) and more major bleeding (31.5 percent vs 20.8 percent; p=0.003). Paravalvular regurgitation was also more frequent (p<0.001), and had an impact on mortality for TAVR patients. For example, 60.8 percent of patients with moderate-to-severe paravalvular leaks and 44.6 of those with mild leaks had died, compared with 35.6 percent of those without regurgitation or trace amounts. While the valves appear to be durable in the long run, physicians were particularly concerned about the high mortality rates. We still have 44 percent mortality at 3 years, said Dr. Bernard Gash of the Mayo Clinic in Rochester, Minnesota, US, who moderated the session. What we have to learn is how better to select these patients. In a press briefing following the presentation, Dr. Patrick OGara of Brigham and Womens Hospital, Boston, however, called attention to the advanced age of the patients 84 years on average. Our expectations for their outcomes need to be tempered by the context in which these procedures are offered. The investigators said PARTNER will continue to follow up on patients for 5 years to assess durability and longer-term outcomes of TAVR.
* PARTNER: Placement of Aortic Transcatheter Valves

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May 2013

Conference Coverage

62nd Annual Scientific Sessions of the American College of Cardiology, 9-11 March, San Francisco, California, US

On- vs off-pump CABG: Patient factors, surgical expertise are key

Naomi Rodrig
hree late-breaking clinical trials compared on-pump versus off-pump coronary artery bypass graft (CABG) surgery, reporting mixed outcomes, according to study population. On-pump CABG is less demanding surgically but more expensive, requiring a heartlung machine and disposable components. Conversely, the less costly off-pump or beating-heart procedure requires a higher degree of surgical expertise. Previous trials comparing the two techniques reported conflicting results, and off-pump procedures have become less popular during the past decade, especially in developed countries. The German Off-Pump CABG in Elderly Patients (GOPCABE) study randomized 2,539 patients aged 75 years undergoing elective, first-time CABG to on- or off-pump surgery. There was no significant difference in the primary composite endpoint of death, stroke, myocardial infarction (MI), repeat revascularization or new renal replacement therapy within 30 days of surgery between the two arms [8.2 vs 7.8 percent; p=0.74], reported Dr. Anno Diegeler of the Heart Center Bad Neustadt, Bad Neustadt, Germany. Results for all components of the primary endpoint were similar between the groups at 30 days, and there was also no significant difference in the rate of the primary endpoint at 12 months (14.0 vs 13.1 percent; p=0.483).

Different types of CABG surgery continue to show mixed outcome results.

Our data showed that CABG can be performed in the elderly population with excellent results, and this is equally true for both techniques. The less costly off-pump surgery may be beneficial in developing countries, he said. CORONARY the largest trial to compare the two procedures examined the composite of death, stroke, MI or new kidney failure in 4,752 patients scheduled to undergo CABG. As reported previously, there was no difference between patients receiving the off-pump and on-pump surgery at 30 days (12.2 vs 13.3

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Conference Coverage
of the primary endpoint among patients receiving the off-pump procedure (9.2 vs 20.6 percent; p=0.028). Furthermore, a significantly higher percentage of on-pump patients required a blood transfusion (80.2 vs 64.9 percent; p=0.017). Our study shows that surgical revascularization without using the heart-lung machine can be beneficial for high-risk patients, especially older ones with many other disorders or diseases, concluded Dr. Jan Hlavicka, of Charles University in Prague, Czech Republic. All investigators stressed that risk assessment and surgical expertise are key factors affecting patient outcomes. Therefore, surgeons should tailor their surgical approach to their technical expertise and expected technical difficulty, suggested Lamy.

percent; p=0.24). We now found that both on-pump and off-pump bypass have similar results even at 1 year, said lead investigator Dr. Andre Lamy of McMaster University in Ontario, Canada. The rates of coronary revascularization were also similar between the groups. While neurocognitive decline might be more prominent with on-pump surgery, the researchers found only a transient improvement in neurocognitive function among those receiving off-pump CABG. At 1 year, our results were similar with both techniques, as was quality of life, he said. In contrast, the single-center PRAGUE-6 trial, which randomized 206 high-risk patients (EuroSCORE 6) to receive on- or offpump CABG, found a significantly lower rate

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May 2013

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Surgery tops medical therapy for obese diabetics

Elvira Manzano
ariatric surgery improved glycemic control better than optimal medical therapy alone in obese patients with type 2 diabetes independent of weight loss, two randomized trials have shown. In the larger of two trials (STAMPEDE*), HbA1c levels normalized to 6 percent by 1 year, the primary endpoint, in 42 percent and 37 percent of patients who underwent gastric bypass and sleeve gastrectomy, respectively, compared with 12 percent in those who received intensive medical therapy alone (p=0.002 and p=0.008). Average weight loss was greater after surgical procedures than after medical therapy (60 lbs vs 10 lbs). Medication use to control lipids, glucose and blood pressure also dropped significantly after surgical procedures, but increased with medical therapy alone. [N Engl J Med 2012;366:1567-1576] STAMPEDE included 150 obese patients (BMI, 27-43 kg/m2) with uncontrolled type 2 diabetes randomized to Roux-en-Y surgery or sleeve gastrectomy, or medical therapy alone. All patients received intensive medical therapy (lifestyle counseling, weight management, glucose monitoring and newer diabetes drugs) prior to randomization. BMI, body weight and insulin resistance improved significantly in those who underwent bariatric surgery. The take home message is that surgical patients enjoyed not only significant or superior improvement in glycemic control but did so on much lower regimens of diabetic and

Bariatric surgery is a treatment option to better manage obese diabetics.

cardiovascular medications, said STAMPEDE study author Dr. Philip R. Schauer from Cleveland Clinic, Ohio, US. In a second trial, bariatric surgery resulted in greater reductions in fasting glucose and HbA1c levels after 2 years than did medical therapy. Seventy-five percent of patients on gastric-bypass and 95 percent on biliopancreatic-diversion (p<0.001 for both) went into remission of hyperglycemia compared with none on medical therapy. [N Engl J Med 2012; 366;1577-1585] Although bariatric surgery was initially conceived as a treatment for weight loss, it is now clear that surgery is an excellent approach for the treatment of diabetes and metabolic disease, said senior study author Dr. Francesco Rubino from Weill Cornell Medical College in New York City, US. The study involved 60 severely obese patients with advanced diabetes randomized to

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News
iatric surgery suggests that they should not be seen as a last resort. Such procedures should be considered earlier in the treatment of obese diabetics. They however cautioned that larger trials of longer duration are necessary to determine durable benefits. [N Engl J Med 2012; 366;1635-1636] Given this concern, STAMPEDE will follow up patients for 4 years.
* STAMPEDE: Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently

conventional medical therapy (medication, strict diet and lifestyle interventions), or gastric bypass surgery or biliopancreatic diversion. Both studies targeted an HbA1c level of <6.5 percent which is more aggressive than the American Diabetes Association standards of 7 percent. In an accompanying editorial, Drs. Paul Zimmet of Baker IDI Heart and Diabetes Institute, Melbourne, Australia and K. George M.M. Alberti of Kings College Hospital, London, said the success of various types of bar-

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May 2013

News

Low melatonin secretion linked to diabetes risk

Radha Chitale
omen who produce low levels of nocturnal melatonin are more than twice as likely to develop type 2 diabetes independent of other major diabetes risk factors, according to a recent observational study. The case-controlled study drew data from a cohort in the US Nurses Health Study and included women who provided urine and blood samples at baseline in 2000. Over 12 years, 370 women developed type 2 diabetes and the researchers matched these subjects with an equal number of controls. [JAMA 2013;309:1388-1396] The researchers measured melatonin secretions indirectly using creatinine as a proxy marker. The median urinary melatonin-tocreatinine ratio among controls was 36.3 ng/ mg, which was higher than the median ratio of the diabetic group (28.2 ng/mg). Women in the diabetes group were divided into three groups of low, medium and high melatonin secretors. The median urinary melatonin-to-creatinine ratio was 67 ng/mg among high melatonin secretors compared with 14.4 ng/mg among the low-secretion group. Women with low levels of nocturnal melatonin were 2.2 times more likely than high melatonin-secreting women to develop type 2 diabetes. The researchers controlled for body mass index, lifestyle and location factors, menopause, history of diabetes, hypertension, use of beta blockers or non-steroidal anti-inflammatory drugs and diabetes biomarkers.

Melatonin may play a role in the pathogenesis of type 2 diabetes.

Lead researcher Dr. Ciaran J. McMullan of Brigham and Womens Hospital, Boston, Massachusetts, US, said the results translated to 9.3 cases of diabetes per 1,000 patient-years among low-secreting women compared with 4.3 cases among high-secreting women. Normally, melatonin levels tend to be low throughout the day, rise in the evening, plateau while sleeping and drop upon waking. Prior studies have shown that insulin resistance and type 2 diabetes is associated with lossof-function mutations in melatonin receptors. McMullan said the data suggests that endogenous levels of melatonin may be part of the pathogenesis of diabetes, however the wide variation in melatonin secretion levels makes unraveling the connection difficult. The question remains as to whether melatonin could be a modifiable risk factor for the prevention or possibly treatment of type 2 diabetes, endogenously through dark exposure or exogenously through oral supplements, the researchers noted. Further studies on different populations, including men and other ethnic groups, may also be indicated.

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May 2013

News

Telehealth not cost-effective, study shows

Radha Chitale
elehealth may not be the cost-saving model of care its been touted as, a new study from the UK shows. Quality of life was no different for chronically ill patients who tacked telehealth measures onto their standard supportive care compared with similar patients who received usual care. Telehealth encompassed digital telemonitoring of patient vital signs, in real time or saved for later access, as well as telephone support, during which healthcare professionals could also monitor and track vitals, and added to the overall costs for patients that received it. The QALY [cost per quality adjusted life year] gain by patients using telehealth in addition to usual care was similar to that by patients receiving usual care only, and total costs associated with the telehealth intervention were higher, the researchers said. A group of 965 patients from a larger telehealth trial were eligible for inclusion in this questionnaire study on health outcomes. These patients had to have at least one of three chronic diseases: chronic obstructive pulmonary disease, heart failure or diabetes. [BMJ 2013;346:f1035] Patients were randomized to telehealth intervention (n=534) or to usual care (n=431). QALY for telehealth plus usual care was 92,000 (S$174,000), which is well above the

UK National Institute for Health and Clinical Excellence threshold of 30,000 (S$57,000), the researchers said. Even factoring in an 80 percent reduction in equipment costs and higher working capacity, analysis showed that telehealth would probably be effective, to 61 percent for a willingness to pay 30,000 per QALY. Telehealth was designed to have a number of benefits to both patient and doctor, including allowing patients to be more independent and spend less time actively seeking monitoring or care. Doctors can monitor patients blood pressure or glucose levels, for example, without scheduling unnecessary visits. These types of measures were thought to reduce healthcare costs through fewer doctor appointments and avoiding unnecessary treatments in favor of more effective ones, particularly for patients with chronic diseases. However, little quality data exist on the association between outcomes and costs. Management of people with long-term conditions is under the spotlight, given the rapidly growing prevalence of such conditions in aging populations, the researchers said. They added that the study raises further issues such as targeting telehealth towards specific subgroups and the effects of livelihood and demographics on telehealth efficacy and costs that should be reviewed in subsequent analyses.

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May 2013

News

Frequent home relocations linked to behavioral problems in some children

Laura Dobberstein

oving to a new home more than three times in the first 5 years of life may increase attention and behavioral problems in economically disadvantaged children, according to a recent US study. Previous studies have linked frequent moving to reduced academic performance, greater rates of high school dropout, poorer emotional and behavioral outcomes and lower levels of educational attainment. Developmental psychologists have shown that the home environment is one of the most important influences on young childrens school readiness, noted study author Dr. Kathleen Ziol-Guest, postdoctoral associate at Cornell University, Ithaca, New York, US, and colleagues. Ziol-Guest and her team examined data of 2,810 American children born between 1998 and 2000 from an existing study on new parents and the welfare of their children. The parents were interviewed at the hospital shortly after giving birth. Follow-up interviews were subsequently conducted by telephone when the child was 1, 3 and 5 years of age. In-home assessments were also done when the child was 3 and 5. The assessments included an interview with the mother, an evaluation of the home environment and an appraisal of the childs health and development. [Child Dev 2013; doi: 10.1111/cdev.12105] At the 5-year assessment, vocabulary and word identification tests determined lan-

guage and literacy outcomes and a checklist monitored behavioral difficulties. Child gender, race, socioeconomic status and parental education level and other demographics were examined. Residential instability was defined as moving at least three times in the first 5 years of a childs life, and poverty was defined by the official federal threshold. Seventy-seven percent of the children in the study had experienced at least one move and 29 percent were residentially instable. Of those defined as having residential instability, 44 percent were below the poverty threshold. Residential instability was linked to attention problems, anxiousness, depression, aggressiveness and hyperactivity among 5-yearolds living in poverty. Language and literacy outcomes and those who were not categorized as poor were not affected by moving. The authors speculated that frequent moves may disrupt a childs socio-emotional development. Social networks may also be disrupted, creating an extra challenge for children to make new friends. Feelings of frustration or anger may be displayed as behavioral problems while test scores are less directly affected. Low-income families may move for different reasons than higher-income families, they explained. While some families choose to move because they are dissatisfied with their old neighborhood or home, others have to move in search of work, less expensive housing, or even due to evictions and foreclosures.

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May 2013

News
for young children, adding that not all children experiencing multiple moves will have behavioral issues. With lower-income families, the stress of financial issues puts burden on the family, which also impacts childrens behavior due to familys stress, said Im-Wang.

Speaking to Medical Tribune, Dr. Sunny Im-Wang, pediatric psychologist and school psychologist in San Francisco, California, US, and author of Happy, Sad, & Everything In Between: All About My Feelings said: Usually, frequent changes and inconsistent environment [are] not good

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May 2013

News

Vitamin D deficiency a concern for kidney transplant patients

Laura Dobberstein
idney transplant patients with vitamin D deficiency should consider taking vitamin D supplements in order to prevent a decline in kidney function, say French researchers. Vitamin D is a critical hormone controlling mineral homeostasis, said Dr. Frank Bienaime of the Universit Paris Descartes and INSERM and Assistance Publique Hopitaux de Paris, France, and colleagues. It promotes phosphate and calcium absorption by the gut and increases calcium reabsorption by the renal distal tubule, thereby providing the positive calcium and phosphorus flux required for bone mineralization. Bienaime and his team studied 634 patients who underwent a kidney transplant to better understand vitamin D levels at 3 months after transplantation. The study examined vitamin D status in relation to early mortality or transplant loss, the efficiency of the kidneys at 12 months as measured by flow rate, and the health of the kidneys measured through scarring and atrophy between 3 and 12 months. The patients were evaluated over a 2- to 4-month period after receiving the transplant. The flow rate of filtered fluid through the kidney, known as glomerular filtration rate (GFR), and vitamin D levels were measured.

Blood and urine samples were analyzed for content and biopsies were examined for tubular atrophy and scarring. [J Am Soc Nephrol 2013; Mar 28. Epub ahead of print] During the course of the study, 19 of the patients were lost to follow-up, 30 patients lost their transplanted kidney, 28 patients died with a functioning transplant, and 3 died after losing their transplanted organ. Infection was the most common cause of death and was seen in 12 patients. Deficiency in vitamin D was shown to correlate with lowered kidney function at 3 months after transplant and increased kidney scarring at 12 months after transplant. Other hormones associated with mineral metabolism like calcium, phosphorus, calcitriol, parathyroid hormone or fibroblast growth factor-23 were not linked to kidney health. Vitamin D deficiency is a common problem among those with impaired kidney function but the status of the hormone after having a kidney transplant is not well understood. The study authors encouraged future research to evaluate the use of vitamin D supplements in kidney transplant patients. [Our results] suggest that maintaining vitamin D concentration within the normal range would prevent renal function deterioration after renal transplantation, said Beinaime. Vitamin D supplementation, a simple and inexpensive treatment, may improve transplantation outcomes.

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May 2013

Drug Profile

Dutasteride/tamsulosin: Combination therapy for BPH

The true prevalence of benign prostatic hyperplasia (BPH) in male populations has been difficult to estimate due to the lack of a standardized definition. However, the characteristic features of BPH abnormal proliferation of stromal and epithelial prostatic cells become more common in men with age. The following article highlights the benefits of dutasteride/ tamsulosin (Duodart, GlaxoSmithKline), a combination treatment consisting of two drugs with complementary mechanisms of action, in patients with BPH.

Naomi Adam, MSc (Med),

Category 1 Accredited Education Provider (Royal Australian College of General Practitioners)

Introduction Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland. Clinically, patients with BPH present with lower urinary tract symptoms (LUTS) either voiding symptoms (eg, weak stream, hesitancy, intermittency and abdominal straining), and/or storage symptoms (eg, frequency, nocturia, urgency and urge incontinence). Voiding symptoms are more common while storage symptoms are more bothersome and interfere more with daily activities. However, not all men with BPH suffer from LUTS, and conversely, not all men with LUTS have BPH. The lack of a standardized definition of BPH means that it is difficult to estimate its true prevalence. In an aging male population ( 80 years), the characteristic histological features of BPH abnormal proliferation of stromal and epithelial prostatic cells are extremely common, seen in up to 80 percent. When present, the symptoms can be extremely bothersome and become more so

over time as the prostate enlarges and the condition progresses. Eventually, complete blockage of the urethra, known as acute urinary retention (AUR), may occur. AUR is a medical emergency that is often unexpected, painful and requires catheterization to treat it. Following a first episode of AUR, the condition often recurs, and 24 to 42 percent eventually go on to have prostatectomy surgery. Guidelines developed at the 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases provide an algorithm for the management of LUTS in men in the primary care setting.

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May 2013

Drug Profile
in the bladder neck, prostate and bladder detrusor. Dutasteride is the only licensed type 1 and type 2 dual 5ARI. [J Clin Endocrinol Metab 2004;89:2179-2184] 5ARIs block the conversion of testosterone to dihydrotestosterone (DH), which is the androgen primarily responsible for hyperplasia of glandular prostatic tissue. This significantly reduces prostate volume in men with BPH. The enzyme 5-alpha reductase is present throughout the body in two forms, or iso-enzymes: type 1 and type 2. Type 1 has been reported to be located predominantly in the skin, both in hair follicles and sebaceous glands, as well as in the liver, prostate, and kidney. Type 2 is found in the male genitalia and the prostate. Clinical efficacy Recently, the CombAT study showed that combination therapy with the -blocker tamsulosin and the 5ARI dutasteride effectively treats LUTS due to BPH. [J Urol 2008;179:616621] The study population consisted of men aged 50 years and over with a clinical diagnosis of BPH by medical history and physical examination. Those with total serum prostate-specific antigen (PSA) greater than 10.0 ng/mL, a history or evidence of prostate cancer, previous prostatic surgery or a history of AUR within 3 months before study entry were excluded from the study. Subjects were randomized to receive either tamsulosin (n=1,611), dutasteride (n=1,623) or the combination of the two agents (n=1,610). There were comparable rates of discontinuation between the three groups, and 79 percent of the population completed the 24-month follow-up visit. The primary endpoint was the self-administered International Prostate Symptom Score

[Male Lower Urinary Tract Dysfunction: Evaluation and Management, 2006] The first step is a series of simple tests, and key among these is the question as to whether patients find their symptoms bothersome. A large proportion of men who present are simply seeking reassurance. Reports in the lay media often erroneously state that getting up to urinate during the night is a sign of prostate cancer, when in fact it is quite normal for older men to get up once per night. For those who are not bothered by their LUTS, no treatment is needed, just reassurance. But in men who do find their LUTS bothersome, individualized medical therapy should be used to address each patients predominant symptoms. There are several pharmacological treatment options that should be used according the underling pathophysiology. [BJU Int 2011;107:1426-1431] Symptoms of overactive bladder are most often treated with antimuscarinic agents. Symptoms associated with obstruction due to prostatic enlargement can be relieved with -blockers. In men with moderate-to-severe LUTS and an enlarged prostate, 5-reductase inhibitors (5ARIs) reduce prostate volume and decrease urethral obstruction, providing continual symptom improvement and reducing the risk of AUR and the need for surgery. Dutasteride/tamsulosin hydrochloride Mode of action Dutasteride-tamsulosin is a combination of two drugs with complementary mechanisms of action to improve symptoms in patients with BPH. [Duodart Prescribing Information] Tamsulosin is an -blocker. Its action is inhibition of sympathetic stimulation via 1-adrenoceptors. This provides relief from LUTS symptoms by relaxing smooth muscle

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May 2013

Drug Profile
after the same meal each day. The effect of renal impairment on the pharmacokinetics of the active compounds has not been studied; however, it is anticipated that no adjustment in dosage would be needed. The medication is contraindicated in patients with severe hepatic impairment, and the effect of mild to moderate hepatic impairment on pharmacokinetics has not been studied. Place within treatment guidelines Guidelines published by the National Institute for Health and Clinical Excellence (NICE) state that men with moderate to severe LUTS should be offered an -blocker. A 5ARI should be offered to men with LUTS who have prostates estimated to be larger than 30 g or a PSA level greater than 1.4 ng/ mL, and who are considered to be at high risk of progression (eg, older men). The combination of an -blocker and a 5ARI is therefore appropriate for men with bothersome moderate to severe LUTS and prostates estimated to be larger than 30 g or a PSA level greater than 1.4 ng/mL. [The Management of Lower Urinary Tract Symptoms in Men. National Clinical Guideline Centre, 2010.]

(IPSS) questionnaire. At month 24, the average ( standard error) decreases in IPSS from baseline were 6.2 ( 0.15) points for combination therapy versus 4.9 ( 0.15) and 4.3 ( 0.15) points for dutasteride and tamsulosin, respectively. Compared with either monotherapy, combination therapy also significantly improved urinary flow rate and reduced prostate volume. Adverse reactions In the CombAT study, the total number of drug-related adverse events (AEs) was higher in the combination therapy group; however, only 5 percent or fewer men withdrew from the study due to an AE. The AEs more common with combination therapy were erectile dysfunction, retrograde ejaculation, altered (decreased) libido, ejaculation failure, decreased semen volume, loss of libido and nipple pain. There were no instances of floppy iris syndrome or breast neoplasms. Dosing The recommended dose of Duodart is one capsule (500 g dutasteride /400 g tamsulosin) taken orally approximately 30 minutes

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May 2013

In Practice
literature, wrist pain is generally subdivided into traumatic or nontraumatic origin. Tendonitis is a common problem that can cause wrist pain and swelling. Wrist tendonitis is due to inflammation of the tendon sheath. Wrist sprains are common injuries to the ligaments around the wrist joint. In the case of tenosynovitis of extensor tendons, there is pain in the dorsum of the wrist that may radiate proximally and distally. There is a history of repetitive activities and overuse. Pain occurs on flexion and resisted extension. Treatment of wrist pain caused by tendonitis usually does not require surgery. In flexor tenosynovitis, pain is located on the palmar aspect of the wrist, is aggravated with wrist motion and with resisted wrist flexion. Carpal tunnel syndrome is the most common compression neuropathy in the upper extremity. In carpal tunnel syndrome, the median nerve is compressed as it passes through the wrist joint. Patients often complain of pain around the wrist, numbness and tingling in the radial three digits, clumsiness and weakness. Patients frequently wake up at night with numbness in the fingers. Tinel test of the carpal tunnel and Phalen test may be positive. Decreased sensibility in median nerve distribution and thenar atrophy are late signs. A cockup wrist splint can be used. Activity modification can be tried in work-related carpal tunnel syndrome. Surgical release of the transverse carpal ligament is performed when non-operative measures have failed, in patients with constant numbness, motor weakness, or increased distal median nerve motor latency noted on electromyography. A ganglion cyst is a swelling that usually occurs over the back of the hand or wrist. These

Managing wrist pain

Dr. Eugene Wong
Consultant Orthopedic & Spine Surgeon Adjunct Assistant Professor Perdana University Graduate School of Medicine Serdang, Selangor, Malaysia

he wrist joint is an area bounded by the distal radius and ulna proximally, and the bases of the metacarpals distally. The joints around the wrist comprise of the distal radioulnar, radiocarpal and midcarpal. Each of the surrounding structures can be the site of injury, degeneration or disease and, thus, a source of pain. The location of wrist pain is indicative of the cause. Patients may present with swelling and pain localized to the radial aspect, dorsal aspect, ulnar aspect, palmar aspect or generalized wrist pain. With careful history taking, thorough physical examination and imaging techniques (plain radiographs, ultrasonography and bone scintigraphy), a diagnosis of the cause of wrist pain can be made in 78 percent of cases. As the wrist can be affected by a multitude of local and general disorders, it is often difficult to make an accurate diagnosis. In the

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In Practice

are benign, fluid-filled capsules. Ganglion cysts are the most common mass on the dorsal surface of the wrist. Most arise from the scapholunate ligament. If the ganglion causes a pain or severely limits activities, the fluid may be drained. Surgery involves removing the cyst as well as part of the involved joint capsule or tendon sheath. Even after excision, there is a small chance the ganglion will return. Scaphoid fracture is most often due to a fall on an outstretched arm. There is tenderness over the anatomic snuffbox. Undisplaced fractures may be casted and a screw fixation done for displaced fractures. Arthritis is a problem that can cause wrist pain and difficulty performing daily activities. Patients with inflammatory arthritis and osteoarthritis involving the radiocarpal, intercarpal and carpometacarpal (CMC) joints present with pain in the wrist. Patients with osteoarthritis may have a history of trauma. Swelling, stiffness and decreased range of motion are present. Radiographs of patients with osteoarthritis show narrowing of the joint space, subchondral sclerosis and osteophytes. Radiographs of patients with inflammatory arthritis show narrowing of joint space, osteopenia, bone erosion and deformity. The arthritic carpal bones can be excised. Joint fusion is done in cases of severe pain. A wrist prosthetic implant is used to maintain pain-free range of motion. De Quervain tenosynovitis is due to inflammation of the first dorsal compartment of the extensor tendons. There is a history of repetitive wrist activities. The Finkelstein test (with thumb flexed into palm, pain is reproduced by ulnar deviation of the wrist) is positive. An anesthetic injection around the tendon sheath can be given. Some patients may require surgical release of the first dorsal compartment.

1. Scaphoid fracture

2. 1st CMC arthritis

3. Kienbocks disease

4. Carpal instability

5. TFCC tear

6. Ulnar impaction syndrome

7. De Quervain tenosynovitis

8. Pseudogout

9. Septic arthritic wrist

10. Ganglion cyst

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In Practice
Radial wrist pain: De Quervain tenosynovitis Scaphoid fracture or non-union Thumb CMC arthritis Radiocarpal arthritis

In cases of distal radioulnar joint instability, pain is located at the distal radioulnar joint, especially with pronation and supination. Pain at the flexor carpi ulnar is usually detected on resisted wrist flexion and ulnar deviation. A triangular fibrocartilage complex (TFCC) tear presents with ulnar-sided wrist pain, often with clicking. Pain is experienced with axial load while rotating the ulnar-deviated wrist. An arthroscopic repair can be done. Immunocompromised patients or those with a history of intravenous drug use are at higher risk of wrist infection than the general population. Pain, swelling, erythema, decreased range of motion (ROM) and other cardinal signs of infection may be present. Increased pain with ROM is characteristic. Elevated leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein are signs of infection. Finding the cause of wrist pain begins with a detailed history, physical examination and the use of several diagnostic tests. X-rays of the wrist are usually a first step and will help determine if more tests are needed. An ultrasound scan can be used to diagnose tendon tears around the wrist. Magnetic resonance imaging (MRI) is commonly used to evaluate the wrist because it can show abnormal areas of the soft tissues. Blood tests are done to look for infection or arthritis. Plain anteroposterior, lateral and oblique radiographs are obtained to look for fracture, with a carpal tunnel view for fracture of the hook of the hamate. A scaphoid view is used to assess scaphoid fracture. MRI may be useful in the diagnosis of TFCC tear and wrist infection. The treatment of wrist pain depends entirely on the cause of the problem.

Dorsal wrist pain: Tenosynovitis of extensor tendons Ganglion cyst Extensor carpi ulnaris tendinitis Ulnar wrist pain: Distal radioulnar joint instability Flexor carpi ulnaris tendinitis Fracture of the hook of the hamate TFCC tear

Palmar wrist pain: Flexor tenosynovitis Carpal tunnel syndrome (CTS) Palmar ganglion General wrist pain: Arthritis Infection
Table 1: Regional distribution of wrist pain.

Mechanical causes: Fracture Non-union of scaphoid or hook of the hamate  Avascular necrosis of the scaphoid (Preisers disease) or lunate (Kienbcks disease). Triangular fibrocartilage complex Distal radioulnar joint subluxation Carpal instability Scapholunate dissociation De Quervains tenosynovitis Intersection syndrome Neoplasm or ganglion Neurologic causes: Distal posterior interosseous nerve syndrome Injury of median nerve (carpal tunnel syndrome) Injury of radial nerve Injury of ulnar nerve (Guyons canal) Thoracic outlet compression syndrome

Systemic causes: Amyloidosis Granulomatous disease (eg, sarcoid, tuberculosis) Hematologic disease (eg, leukemia, multiple myeloma)  Metabolic conditions (eg, acromegaly, diabetes, gout, hyperparathyroidism, hypocalcemia, hypothyroidism, Pagets disease, pregnancy, pseudogout). Osteomyelitis Peripheral neuropathy  Reflex sympathetic dystrophy (complex regional pain syndrome).  Rheumatologic disorders (eg, psoriasis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus).
Table 2: Etiology of wrist pain.

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In Practice
Anti-inflammatory medication: Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly prescribed medications, especially for patients with wrist pain caused by arthritis and tendonitis. Cortisone injections: Cortisone is used to treat inflammation which is a common problem in patients with wrist pain. Some wrist conditions require arthroscopy for diagnosis or treatment. Arthroscopic surgery is a treatment option available for some causes of wrist pain such as TFCC tear and arthritis. In cases of severe pain arising from arthritis, wrist replacement or fusion may be required. A detailed history taking, clinical examination and appropriate imaging will identify the cause of wrist pain. Diagnostic injections are sometimes needed.

Rest and activity modification: The first treatment for many common conditions that cause wrist pain is to rest the joint, and allow the acute inflammation to subside. It is important, however, to use caution when resting the joint because prolonged immobilization can cause a stiff joint. Adjusting activities so as not to irritate the joint can help prevent worsening of wrist pain. Ice and heat application: Ice packs and heat pads are among the most commonly used treatments for wrist pain. Wrist support: Support braces can help patients who have either had a recent wrist sprain injury or those who tend to injure their wrists easily. These braces act as a gentle support for wrist movements. They will not prevent severe injuries, but may help the patient perform simple activities while rehabilitating from a wrist sprain.

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May 2013

After Hours

Getting Around on the

Joseph Hoye
here may be bigger and there may be busier, but no one can deny the London Underground its place in history as the worlds first underground rail system. It has inspired poetry, featured in films and been the subject of countless documentaries and magazine articles. Reviled occasionally, praised sporadically, it is the pulsing artery of a sprawling city that depends on mass transit to stay alive. For most Londoners, it is just a fact of life. To visitors, it can be fascinating, horrifying and rewarding often within the same journey. One hundred and fifty years ago, the worlds first underground railway opened. The Metropolitan Railway hauled 38,000 passengers on its first day in January 1863, traveling the 6 kilometers between Paddington and Farringdon. A broad gauge railway, the locomotives were steam powered and the wooden carriages were illuminated by gas lamps.

London Underground

Jump forward to today. From that single line of 6 kilometers, there now runs 402 kilometers of electrified track with trains servicing 270 stations across 26 London boroughs and into neighboring counties. Its history and culture is rich. Ghosts abound, civilians took shelter during bombing raids, US talk-show host Jerry Springer was born in the Underground. Theres even a book chronicling the mice of the Underground. Ever wondered which station you keep seeing in London film sets? Good odds that its the disused Aldwych station on the Piccadilly line. Patriot Games, V For Vendetta and Atonement are amongst the many films to use this station. Using the Tube With its bustling 3.5 million passengers each day, it can be difficult to negotiate the Tube. It may seem like chaos but the London Underground does have an etiquette that helps keep the system moving. Some of these

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After Hours
pram-friendly. Its not uncommon to have a set of three or four stairs to negotiate along walkways, seemingly for no reason. And not all stations have step-free access onto the carriages. If in doubt, it pays to check the Tube map to see which stations have the best access. If theres one thing every visitor to London needs, its the free Tube map. There are plenty of apps that do the job but the modern version of Harry Becks 1933 design classic is a life saver. The fold-up illustration handily fits inside a wallet or pocket, is color-coded to reduce confusion and clearly shows the junctions where passengers can change lines. That said, never use it to work out the distance needed to get to your destination. The stations are arranged to fit on a small sheet of paper; thus, two adjacent stations may be anywhere from 500 meters to 5 kilometers away from each other. Pick up a copy from any Underground station. Of course the whole point of the Underground is to move people quickly around a large city that was never designed for railways, let alone motorways. Most of Londons key sites of interest are within Transport Zones 1 and 2 and it would not be inconceivable to visit Buckingham Palace, Westminster, London Eye, the Shard, the Tower of London and Hyde Park in one day if travelling on the Tube. Heathrow: check. St Pancras International (Eurostar): check. London City Airport: check. Waterloo Station: check. London is spoiled for choice when it comes to long distance travel options and each is easily reached via the Underground. The Tube journey from Heathrow to the City may be time consuming but is worth considering if

guidelines are written on the walls throughout the maze of pedestrian tunnels but generally theyre just common sense. U  nless signage declares otherwise, keep to the left side of station walkways.  On escalators, walk on the left, stand on the right side and remain in single file.  Stand aside to allow passengers off carriages before you enter.  If you are travelling in a group, remain alert to people trying to walk at a faster rate than you. Let them pass.  Food and drink are permissible in stations and on trains but alcohol and smoking are not.  Oyster Card users must touch in and out or risk a fine. On Sundays, barrier arms at some stations may be raised; users must still touch cards to the terminals. I  f possible, move into the center of the carriage youre traveling on. Buying tickets for the Tube is very simple. Most stations have a series of automated booths that take cash or card. Options are for single fares, day passes, weekly or monthly cards. If youre going to be traveling extensively, consider an Oyster card. Not only does it automatically discount fares, bus trips are included in the weekly/ monthly options. Like any transport option, the Underground gets very busy at certain times of the day. If at all possible, avoid traveling on weekdays before 9:30am or between 5pm to 6:30pm. And if you do have to travel at these times, be prepared to have two or three trains pass by before you get on. The London Underground is an old rail system. While many stations have lifts or escalators, some are neither wheelchair nor

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After Hours
moored on the river, is particularly daunting when seen from the deck of a ferry. And it is easy to walk the streets of London. Wandering a 500 meter radius around Trafalgar Square nets the National Gallery, Downing Street, Horse Guards, Piccadilly Circus, Leicester Square, Covent Garden and the Thames. Sometimes, Shanks pony is the best way to get around London but for the rest of the time, choose the Tube. London has much to offer, whether you live there or are just passing through for a few days. Theaters, restaurants, football, museums: all are world class and all owe a debt to the Underground. It is as much a part of the city as the Tower of London or Tate Britain and is rightly celebrating 150 years of service. Used to get from A to B or enjoyed in its own right, the Tube is Londons underground superstar.

the Heathrow Express is out of action or the motorways are snarled up. London isnt just the inner city. Harrow, Kew Gardens, Wimbledon and Europes largest shopping centre Westfield Stratford are all directly accessible via the Tube. There are occasions when the Underground is not a travel option. London also has a very good overland rail service as well as an excellent bus service - some of the bus routes operate a 24-hour service. Do not discount Londons famous black cabs as a way to move around the city but do be aware that longer trips can be somewhat pricey and traffic holdups can last several hours. Finally, the River Thames is also a great option for anyone wanting to move quickly or see many of Londons famous landmarks. HMS Belfast, originally a light cruiser for the Royal Navy and now a museum ship permanently

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May 2013

After Hours

Biking the

Golden Gate Bridge

Radha Chitale

he Golden Gate Bridge cuts a russet swoop across the San Francisco skyline. Completed in 1937 to connect the main part of the city to its rapidly expanding northern counties, the bridge has always been open to pedestrian traffic. Graced with sunny weather on a recent trip to San Francisco, I thought the best way to experience this icon of modern architecture up close would be a leisurely cycle. I started at Fishermans Wharf, the center of San Franciscos historical fishing district and a popular tourist spot. The staff at Blazing Saddles, a bicycle rental company, outfitted me with a bike, helmet, lock and water, and mapped out what would be a 13-kilometer ride hugging the San Francisco Bay, across the bridge and down to Sausalito in Marin County where I could

catch a ferry back to the city. The whole ride would take about 2-and-a-half hours. The route to the bridge is mostly flat but there are several steep hills that I, less than toned through the quadriceps, had to walk up. The first incline came almost immediately after I set off from Hyde Street. Pushing my bicycle up the hill did give me time to admire a clear view of the bay and Alcatraz Island, once the site of the famous high-security prison. Beyond that first very short hill was Fort Mason Green and further, Crissy Field, the northern edge of The Presidio park. The quiet, green ride required no great effort, so I took my time, snapping too many photos of sailboats cutting through the bay. Having rested sufficiently, I chose not to attempt the next and steepest portion of the ride as the path climbs upwards in order to

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May 2013

After Hours
With just enough time for a restorative coffee, I caught the last ferry back to the Port of San Francisco. I hopped on my bike again and cycled up the Embarcadero back to Fishermans Wharf to return it, 4 hours after I began.

go from sea level to the base of the bridge 67 meters above, and instead enjoyed watching more able cyclists chug past me. The distinctive orange bridge loomed large as soon as I crested the hill, a span suspension design in which the roadway hangs off vertical suspenders attached to cables strung between 227-meter high towers. The simple railings, vertical ribbing and diminishing towers are hallmarks of art deco style, popular in the 1930s. The whole structure looks delicate from afar but the main cables are almost 1 meter in diameter and the total weight of the bridge is over 800,000 metric tons. I made my way under the bridge to the west side where cyclists could get on the footpath. Safety signs warn about high winds while crossing; but while the winds did not interfere with my balance, I certainly could have used some gloves and an extra sweater under my down vest. My discomfort was more than compensated by the expanse of the Pacific Ocean and the gentle green hills of Marin County. Some care is necessary when riding, as there are several blind turns as the footpath curves around the main towers, but small outcroppings of footpath allow a place to rest or take pictures clear of passing cyclists and pedestrians. The gradual incline I felt as I pedaled started to give as soon as I passed the halfway point and I quickly reached the far side of the bridge. Out of the sun it was chilly and I debated continuing on to Sausalito, an unknown route, or head back the way I came. A fellow cyclist advised me to continue on and catch the ferry, saying it was an easy 20-minute ride. In the future, I will be more wary of pro-looking cyclists in bright yellow biking shorts who tell me a hill is not big because once again I found myself pushing my bicycle uphill. However, the subsequent coast into picturesque Sausalito was enjoyable.

Did You Know?

The Golden Gate Bridge has always been painted International Orange, chosen to complement the warm colors of the surrounding land masses and contrast with the cool blues of sea and sky, which also makes it more visible to passing ships through the Bay fog. The bridge towers have fewer lights towards the top to appear more majestic at night, as if they soared beyond illumination. The Golden Gate Bridge was only the longest suspension bridge in the world until 1964, but it is still the most photographed bridge in the world. The bridge can expand or contract by up to 16 feet when the temperature changes. It has appeared prominently in a number of films including Superman (1978), Interview with a Vampire (1994) and The Rock (1996).

36

May 2013

Humor

I think, if you loosen your belt a little, you wont be experiencing those terrible chest pains!

I know you must be in a lot of pain, but lets be totally fair. This is your night to do the dishes!

Dont try to hide under those masks. I know who you are!

She can forgive Lance Armstrong but she cant forgive me!

Just make sure you dont take these sleeping pills and a laxative on the same night!

Whatever it is going around, you have it!

37
May

May 2013

Calendar
American Society of Clinical Oncology Annual Meeting
31/5/2013 to 4/6/2013 Location: Chicago, Illinois, US Info: ASCO Customer Care Tel: (1) 888 282 2552 or (1) 571 483 1300 Website: http://chicago2013.asco.org

American Urology Association (AUA) Annual Meeting

4/5/2013 to 8/5/2013 Location: San Diego, California, US Info: AUA Tel: (1) 410 689 3700 Fax: (1) 410 689 3800 Email: customerservice@AUAnet.org Website: www.aua2013.org

World Congress of Nephrology

31/5/2013 to 4/6/2013 Location: Hong Kong Info: ISN World Congress of Nephrology 2013 Tel: (852) 2559 9973 Fax: (852) 2547 9528 Email: registration@wcn2013.org Website: www.wcn2013.org

46th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
8/5/2013 to 11/5/2013 Location: London, England Info: ESPGHAN Organizers Tel: (44) 845 1800 360 Email: ESP2013-Reg@mci-group.com Website: www.espghan2013.org

JUNE
23rd Conference of the Asian Pacific Association for the Study of the Liver
6/6/2013 to 9/6/2013 Location: Singapore Info: APASL Secretariat Email: apaslconference@kenes.com Website: www.apaslconference.org

9th Asian Society for Paediatric Research Congress

9/5/2013 to 12/5/2013 Location: Kuching, Malaysia Info: ASPR-PSM 2013 Congress Secretariat Tel: (603) 4023 4700, 4025 4700, 4025 3700 Website: www.aspr-psm2013.org

International Digestive Disease Forum 2013

8/6/2013 to 9/6/2013 Location: Hong Kong Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 Fax: (852) 2559 6910 Email: info@iddforum.com Website: www.iddforum.com

20th European Congress on Obesity

12/5/2013 to 15/5/2013 Location: Liverpool, England Info: ECO2013 Secretariat Tel: (44) 20 8973 2506 Email: enquiries@easo.org Website: www.easo.org/liverpool-eco-2013

Diabetes Preventing the Preventables Forum

24/5/2013 to 26/5/2013 Location: Kuala Lumpur, Malaysia Info: Asia Diabetes Foundation Tel: (852) 2637 6624 Fax: (852) 2647 6624 Email: enquiry@adf.org.hk Website: www.adf.org.hk/dpp2013

3rd World Congress of Thoracic Imaging

8/6/2013 to 11/6/2013 Location: Seoul, Korea Info: WCTI Secretariat Tel: (82) 2 3452 7245/(82) 2 3471 8555 Fax: (82) 2 521 8683 Email: wcti2013@insession.co.kr Website: www.wcti2013.org

12th Congress of the European Association for Palliative Care

30/5/2013 to 2/6/2013 Location: Prague, Czech Republic Info: European Association for Palliative Care Tel: (49) 89 548234 62 Fax: (49) 89 54823443 Email: eapc2013@interplan.de Website: www.eapc-2013.org

17th International Congress of Parkinsons Disease and Movement Disorders

16/6/2013 to 20/6/2013 Location: Sydney, Australia Info: MDS Congress Staff Tel: (1) 414 276 2145 Fax: (1) 414 276 3349 Email: congress@movementdisorders.org Website: www.mdscongress2013.org

38

May 2013

Calendar
13th Asian Federation of Sports Medicine Congress
25/9/2013 to 28/9/2013 Location: Kuala Lumpur, Malaysia Info: AFSM Organizers Email: 13afsm@gmail.com Website: www.13afsm.com

American Diabetes Association 73rd Scientific Sessions

21/6/213 to 25/6/2013 Location: Chicago, Illinois, US Info: ADA Registration Customer Care Center Tel: (1) 415 268 2086 Email: ADAReg@cmrus.com Website: http://scientificsessions.diabetes.org

upcoming
9th Asian Dermatological Congress
10/7/2013 to 13/7/2013 Location: Hong Kong Info: ADC 2013 Secretariat Tel: (852) 3151 8900 Email: adc2013@swiretravel.com Website: www.adc2013.org

13th International Workshop on Cardiac Arrhythmias - VeniceArrhythmias 2013

27/10/2013 to 29/10/2013 Location: Venice, Italy Info: VeniceArrhythmias 2013 Organizing Secretariat Tel: (39) 0541 305830 Fax: (39) 0541 305842 Email: info@venicearrhythmias.org Website: www.venicearrhythmias.org

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