Experts fear rise of drug-resistant superbug

Medical Tribune January 2009 P1&6
David Brill

Rising levels of drug resistance among Acinetobacter Baumannii are causing serious concern among infectious disease experts, who are calling for urgent international attention to the issue.

The bug is particularly prevalent in hospitals in Southeast Asia, with Taiwan and Korea seemingly the worst affected.

The rapidly dwindling number of treatment options could soon herald the dawn of the “post-antibiotic era,” according to a specialist from Singapore, where extensively drug-resistant strains have already been reported.

A. Baumannii resistance rates are increasing globally, with around half of strains presently thought to be resistant to at least one antibiotic. Nearly 20 percent of strains are resistant to all but one or two agents.

Reports have already emerged of pandrug resistant strains, which – although rare at present – will beome increasingly common if the problem is not addressed, said Professor Matthew Falagas, an international expert who published a recent high-profile review calling for more research into treatment options. [Lancet Infect Dis 2008 Dec;8(12):751-62]

“We should be worried because we have never heard before of bugs which affect humans where we do not have an antibiotic to provide,” he told Medical Tribune.

“The issue of pan-drug resistance needs international attention. Public health organizations and local infection controls at the country level should disseminate guidelines on this issue,” he said, adding that in some hospitals the significance of the bug is already on a par with methicillin-resistant S. Aureus (MRSA).

A. Baumannii mainly affects seriously ill patients in intensive care units and burn wards. Although less common than other hospital-based infections, the bug can cause significant morbidity and mortality, placing a heavy drain upon hospital resources through repeated hospitalizations and increased lengths of stay.

A Singapore study found that 69 percent of A. Baumannii strains in one intensive care unit were resistant to carbapenem. Nearly 20 percent of isolates from all the nation’s hospitals were resistant to everything except the polymixins, which can cause significant toxicity to the brain and kidneys. [Emerg Infect Dis 2007 Dec;13(12):1944-7]

“Its ability to acquire resistance is a big concern because there aren’t going to be many treatment options available,” said Dr. Tan Thuan Tong, an infectious diseases consultant at Singapore General Hospital.

“We foresee a time when you get strains that are not treatable and you just try your luck with various combinations that might act in a synergistic manner,” he said, adding that such a scenario could arise in Singapore within the next 5 years.

Around 30 to 40 percent of patients who get a multidrug-resistant A. Baumannii bloodstream infection may die, according to Tan, but he added that the directly attributable mortality is not clear-cut since patients are often critically ill for other reasons.

Falagas, meanwhile, called on hospitals worldwide to decrease the usage of antibiotics and promote stricter infection prevention and control measures, particularly with regard to hand hygiene. He added that research is now ongoing to find new antibiotics for Gram-negative bacteria, but said that the process has been too slow getting started.

“The scientific community and the pharmaceutical companies have focused attention on Gram-positives without understanding the significance of Gram-negatives as healthcare-associated infections, and especially A. Baumannii,” said Falagas, who is director of the Alfa Institute of Biomedical Sciences in Athens, Greece, and an adjunct associate professor at Tufts University
School of Medicine, Boston, US.

Singapore has already begun to acknowledge the growing problem of antimicrobial resistance, with a group of experts publishing a recent position paper advocating stricter controls on the use of antibiotics. [Singapore Med J 2008 Oct;49(10):749-55]

“In the 18th and 19th century, there were no antibiotics and treatment was with drainage of pus, amputation and other surgical approaches. If you have infections with these untreatable bugs, then you are back to the days when you can’t do anything,” added Tan.

hsCRP: A new player on the cardiovascular risk stratification stage

Medical Tribune January 2009 P2&3

Dr. Jacques Genest, director of cardiology and Novartis Chair in Medicine at McGill University, Montreal, Canada, addresses the emerging role of high-sensitivity C-reactive protein in predicting cardiovascular risk.

High-sensitivity C-reactive protein (hsCRP) represents a new paradigm in the assessment of cardiovascular risk. It is set to become the first new biomarker for 30 years to be incorporated into routine clinical practice alongside traditional tests such as blood pressure and cholesterol. Guidelines across the world are under review, and it is only a matter of time before hsCRP becomes an integral tool in the risk stratification armory of the primary care physician.

The recent Justification for the Use of Statins in Prevention (JUPITER) trial showed that treating patients who had elevated hsCRP in the absence of other risk factors could significantly reduce the incidence of major cardiovascular events. After a median of 1.9 years of follow-up, the occurrence of cardiovascular death, myocardial infarction, stroke, arterial revascularization or hospitalization for angina was reduced by 44 percent in those treated with rosuvastatin (20mg daily). [N Engl J Med 2008 Nov 20;359(21):2195-207]

These results do not justify testing everyone for hsCRP, but rather suggest that the test will be of great benefit for patients who occupy the grey area between low and high risk. A high hsCRP score can push a debatable case over the treatment threshold while a low score, conversely, can confirm that the patient does not require treatment. Those already deemed to be at high-risk should receive treatment regardless of hsCRP, so the test will add little prognostic value in these patients, while at the other end of the scale there is not sufficient evidence to support routine hsCRP testing in young, healthy people with no other risk factors.

Physicians should begin, therefore, by performing a full and complete cardiovascular risk stratification including sex (until menopause in women), age, physical activity levels, diet, diabetic status, blood pressure and LDL, HDL and total cholesterol levels. For patients who are not obviously at high or very low risk, the physician should now routinely include an hsCRP test. Present evidence suggests that this strategy should be adopted in all men aged over 50 and women aged over 60 – the population that was successfully targeted for treatment in JUPITER. In my opinion, hsCRP will ultimately prove to be of use in men aged over 40 and all postmenopausal women, since these years often herald an increasingly sedentary lifestyle whereby the long-term outcome is likely to be heart disease or cancer. We await the support of local guidelines on this point, however, and at present physicians should exercise their own judgment as to the appropriate age for introducing hsCRP testing.

JUPITER treated patients with hsCRP levels of 2.0 mg/l or higher, and physicians may wish to adopt this level as their cut-point for deciding whether to initiate treatment. There is, however, strong epidemiological data and an ongoing argument in support of adopting a threshold of 3.0 mg/l or higher. This, again, will prove a matter for the guideline makers to decide and is likely to vary from country to country. For those with socialized medicine the cost implications of adopting the lower threshold will be considerable, and will prove an important factor in this decision.

Introducing routine hsCRP testing will undoubtedly increase the number of patients being treated with statins. We must not lose sight, however, of the continued importance of diet and lifestyle interventions, for which there is incontrovertible evidence in favor. Physicians should continue to press the message on five fronts: smoking cessation, quality of diet, quantity of diet, daily exercise, and serenity. The latter encompasses both stress management and levels of social interaction – both important prognostic factors in long-term mortality outcomes. Addressing these issues in a single consultation can be difficult – particularly when seeing the patient only once every 6 to 9 months – and I would recommend that GPs refer certain cases to a dietician and kinesiologist in order to improve motivation through more regular advice and feedback.

Many biomarkers have come and gone over the past 20 years of my research career but very few have proven to be clinically useful. Homocysteine, inflammatory factors, cell adhesion molecules, matrix metalloproteinases, and enzymes such as lipoprotein-associated phospholipase A2 have all failed or are still not ready for primetime use. These markers may predict disease but that does not mean that targeting them will automatically yield a reduction in hard clinical trial endpoints.

The journey towards hsCRP testing has been a long one but the marker has finally matched our ability to predict with our ability to prevent, while also asserting its independence from other risk factors. Guidelines will change in time, but in the face of the evidence from JUPITER physicians may decide not to wait. The time is right, in my opinion, to begin measuring hsCRP and implementing the appropriate strategies in the JUPITER-like patient while we await further international guidance. Unlike other biomarkers, hsCRP testing is here for good.

Dr. Genest is one of the investigators of the JUPITER trial and reports receiving consulting fees from AstraZeneca, Merck, Merck Frosst, Schering-Plough, Pfizer, Novartis, Resverlogix and Sanofi-Aventis.

Placebo prescriptions leave patients in the dark

Medical Tribune January 2009 P4
David Brill

US physicians regularly prescribe placebo treatments but are rarely open with their patients about doing so, a recent study suggests.

Sixty-two percent of physicians who completed a postal survey said that prescribing placebos was ethically permissible, and almost half reported doing so at least 2 or 3 times per month.

However just 5 percent of those who gave placebos said that they explicitly described them as such to their patients. The majority – around two thirds – usually described the treatment as a medicine which is not typically used for that particular condition but which might be of benefit.

“Our study seems to suggest that doctors may be using placebo treatments and they may be cutting corners in terms of how they describe them to patients,” said lead researcher Dr. Jon Tilburt, currently an assistant professor of medicine at the Mayo Clinic, US.

“I don’t think that these data show that doctors are actively deceiving their patients all the time,” he added, noting that the use of truly ‘inactive’ placebos was reported by less than 3 percent of the respondents.

“Physicians rarely use treatments such as sugar pills or saline in which there is no evidence that it could even possibly have a physiological benefit. Those treatments, I think, would be more closely aligned with overt deception,” he said.

Over-the-counter painkillers and vitamins were the most common choices of placebo in the study, with 41 and 38 percent of physicians, respectively, having recommended these treatments in the past year. Sedatives and antibiotics had each been recommended by 13 percent of physicians during that time.

Although the study did not address the complex issues that underlie physicians’ motivations for prescribing placebos, Tilburt believes that in general they have their patients’ best interests at heart when doing so.

“Physicians have a deep impulse to help but when you put them in a circumstance where they cannot fully realize that impulse they still want to do something, even if it comes at some expense to informed consent. And because we don’t have a healthcare system that reimburses for reassurance, good conversations and a quality relationship, we sometimes substitute pills for those more existential aspects of our caring,” he said.

Dr. Thiru Thirumoorthy, a former director of the Singapore Medical Association’s Centre for Medical Ethics and Professionalism, said that placebos have historically been an acceptable part of the healing process in all cultures – particularly among eastern traditions. He noted, however, that doctors need to exercise their judgment before prescribing placebos and must be able to show that they have acted in the patient’s best interests when called to account.

“Placebos must not cause harm, should not take the place of other effective medications, and should not be used unless all other proven treatments have been exhausted or are contraindicated,” he said.

“Placebos should not be used to create a dependency situation. Patient empowerment must be promoted in diseases that do not have effective treatments.”

The survey by Tilburt et al. was completed by 679 practicing rheumatologists and general internists. The researchers defined a placebo as “a treatment whose benefits (in the opinion of the clinician) derive from positive patient expectations and not from the physiological mechanism of the treatment itself.” [BMJ 2008 Oct 23;337:a1938. doi: 10.1136/bmj.a1938]

Future research is directed at understanding whether the power of the placebo effect can be harnessed without keeping patients in the dark, Tilburt said.

“There is some suggestion that even when we tell patients that they’re going to get a placebo there is still some placebo benefit. There’s probably some detriment in the degree of efficacy when you eliminate deception but it’s not totally eliminated, which is fascinating.”

Voluntary counseling could help doctors avoid burnout

Medical Tribune January 2009 P5
David Brill

Short counseling sessions can reduce burnout among doctors and encourage them to make positive changes to their working lives, a new study suggests.

Doctors who volunteered for an intervention program in Norway reported lower levels of emotional exhaustion, worked fewer hours per week and were less likely to be on full-time sick leave a year later.

They were also more likely to seek further professional help, with 53 percent having undergone psychotherapy at 1-year follow-up compared to just 20 percent at the time of enrollment.

Many had already reached high levels of distress and had considered attending the program for quite some time before actually doing so, according to Dr. Karin Rø of the University of Oslo, who led the study.

“The program legitimizes the need for doctors to take a step back for a while and think about their situation,” she said.

“A lot have come back to me and said that it was really important at that time in their life to have somebody to talk to, to get a different perspective on their own situation. Giving a little help, in time, is much better than having to give a lot of help when the situation is much worse.”

Volunteers at Villa Sana – the only center of its kind in Norway – chose between a single one-on-one counseling session of around 6 hours, or a week-long course involving daily lectures followed by group discussions. All sessions were confidential and no medical records were kept. A total of 227 doctors were included in the study, 185 of whom completed 1-year follow-up questionnaires. [BMJ 2008 Nov 11;337:a2004]

Dr. Sim Kang, a consultant psychiatrist at the Institute of Mental Health, Singapore, hailed the research as an important reminder of a timely issue.

“The healthcare profession is certainly susceptible to the onset of burnout if one is not careful about it. The demands of the job are changing and the expectations are quite high from the public nowadays,” he said.

“The symptoms of burnout encroach not just upon the sense of physical tiredness but also the sense that one is mentally wearied and emotionally drained. The message is that if prevention isn’t working and things are getting out of hand then they should seek help.”

Another BMJ study published this year reported that depressed pediatric residents made six times as many medication errors per month as non-depressed residents. [2008 Mar 1;336(7642):488-91]

Rø pointed to this finding as evidence that doctors need to take care of their own wellbeing in order to take care of others.

“When you fly on a plane and the oxygen masks come down you’re supposed to put your own one on before you help anyone who needs it. I think that’s a very good picture of doctors,” she said, adding that she hopes the study will prompt the creation of other similar centers in future.

A year on from the intervention the participants had reduced their mean working hours by an average of 1.6 hours per week. Just 6 percent were on full time sick leave, compared to 35 percent at baseline.

High rates of depression and suicide have been well documented among doctors. A recent study of Brazilian medical students found that as many as 38.1 percent had depressive symptoms, with females particularly susceptible. [BMC Medical Education, in press]

Rø noted that the Norwegian counseling intervention helped the doctors to normalize their situation, having previously felt that they were the only ones experiencing such feelings of distress. They often fail to seek help because they are used to focusing solely on the needs of their patients and do not realize when they are in need of help themselves, she said.

The exact prevalence of depression among the medical community in Asia is largely unknown.

However, Sim encouraged doctors to discuss their feelings of stress and anxiety in informal support groups with their peers whenever possible, adding that he would like to see longer-term data on the sustainability and generalizability of the Norwegian model before advocating the adoption of more formal, structured programs.



Seven tips for avoiding burnout

Dr. Sim Kang, a consultant psychiatrist at the Institute of Mental Health, Singapore, offers his advice on how to de-stress before it gets too late.

1 – Acknowledge and accept that we are all equally vulnerable and can feel trapped and overwhelmed like anyone else. Medical professionals are not superheroes.

2 – Be willing to communicate with others, particularly through informal networks of colleagues, family and friends.

3 – Clarify your responsibilities within the job and resolve any ambiguities that may be causing additional stress.

4 – Determine your own strengths and weaknesses and play to them.

5 – Educate yourself about the symptoms of burnout.

6 – Find time off to unwind and relax.

7 – Group together with your peers to discuss the difficult issues and identify any problems you may be experiencing.

New Singapore heart center offers one-stop shop for multidisciplinary care

Medical Tribune January 2009 SFVI
David Brill

The National University Heart Centre, Singapore (NUHCS), is set to provide a one-stop treatment shop for cardiac patients, the center’s director said recently.

The ongoing redevelopment project will bridge the gap between cardiologists and other specialists within the National University Healthcare System, enabling multiple comorbidities to be treated in just one hospital visit, Associate Professor Tan Huay Cheem told a press conference.

The NUHCS is presently undergoing a sizeable expansion which will also strengthen ties between scientists and clinicians through the creation of a new translational research-focused Cardiovascular Research Institute.

An additional 25,000 outpatient procedures will be performed annually at the NUHCS by 2015 – a projected 45 percent increase on the current capacity of 55,000. The center is due to move into dedicated new facilities by the end of next year, with overall floor space rising around 50 percent and the size of the outpatient clinics increasing threefold by 2011.

Once completed, the NUHCS will focus on four key areas of cardiovascular care: acute coronary syndromes, heart failure, congenital heart disease and vascular medicine.

“Cardiac patients nowadays don’t just have cardiac conditions – they will frequently have other illnesses such as diabetes, kidney failure, or even mental conditions such as depression or anxiety,” said Tan.

“The current arrangement most of the time is that patients will have to come back repeatedly for follow up. What we want to do here is create a one-stop sort of experience where patients could see as many specialists as they need in a single visit.”

Pediatrics, obstetrics and gynecology, respiratory medicine and anesthesia are among the other designated departments which are expected to work more closely with the redeveloped cardiology center. A new division of cardiovascular nursing is also being created as part of the initiative.

Among the planned research projects is the development of a Singapore-specific cardiovascular risk prediction model, said Tan, noting that this will enable doctors to better direct their resources and thereby improve patient outcomes. A state-of-the-art chronic disease management program will also be created as part of the heart failure initiative.

“The vision that we have for the new heart centre is to shape medicine for the future. The mission is to advance health by integrating excellent clinical care with research and education, and the values of our new heart centre will be teamwork, respect, integrity, compassion and excellence,” added Tan.

The expansion is expected to increase the number of doctors at NUHCS by 20 percent and the nurse workforce by 10 percent. The centre will remain on the Kent Ridge campus, housed in a new building on the site of the current dental school.

Cardiovascular disease is currently the second most common cause of death in Singapore and the burden continues to increase. The number of cardiac outpatient visits each year currently stands at around 200,000 nationwide but is projected to rise to 320,000 by 2015.

The NUHCS alone discharged 7,200 inpatients in 2008 but expects this number to reach 10,000 within 7 years. The number of heart attacks treated at the centre almost doubled between 2000 and 2006.

A new dedicated cancer institute is also due to be opened soon by the National University Healthcare System, which comprises the National University Hospital and the National University of Singapore’s Yong Loo Lin School of Medicine.

The NUHCS has been operating since August 2007 within the existing cardiology facilities at the National University Hospital. It is Singapore’s second national cardiac facility, alongside the National Heart Centre at the Outram Park campus.

Gefitinib reduces toxicity for advanced lung cancer patients

Medical Tribune January 2009 P11

David Brill

Gefitinib is a viable second-line alternative to chemotherapy for advanced non-small-cell lung cancer, offering similar survival rates with fewer side effects, a large-scale international study has shown.

The drug represents “an important shift in the treatment paradigm for this disease,” the authors of the INTEREST* trial reported in The Lancet. [2008 Nov 22;372(9652):1809-18]

Patients who took oral gefitinib also had improved quality of life compared to those who received intravenous infusions of docetaxel.

Asian patients, women, non-smokers and patients with adenocarcinoma all had longer survival with gefitinib – echoing the findings of previous trials which have shown the drug to be of particular benefit in these subgroups. Unexpectedly, however, INTEREST also found similar survival patterns with docetaxel, suggesting that these may be generally-applicable prognostic factors unrelated to the specific treatment.

Gefitinib is not currently approved for routine use by the US FDA. However in some Asian countires it is authorized for second-line use. For example in Singapore patients are typically given a choice between second-line treatment options in the event that initial chemotherapy is unsuccessful.

“Should the patient go on to further chemotherapy or should they go on to other drugs like gefitinib? This study confirmed that gefitinib is just as good as chemotherapy but may have fewer side effects,” said Dr. Toh Chee Keong, a consultant medical oncologist at the National Cancer Centre Singapore (NCCS).

Given the choice, most patients prefer an oral drug to chemotherapy but the higher cost of gefitinib can sometimes be a prohibitive factor, he said.

It remains unclear exactly who will benefit most from each treatment and why, he added, but noted that in his experience a non-smoking status is the most powerful predictor of a positive response to gefitinib.

In contrast to previous trials, neither epidermal growth factor receptor (EGFR) gene copy-number nor EGFR protein expression predicted survival with gefitinib in INTEREST.

The study is one of the few phase III clinical trials to directly compare the efficacy of docetaxel with an EGFR tyrosine kinase inhibitor. The analysis included 1,433 patients who had not responded to previous chemotherapy, recruited from 149 centers in 24 countries between March 1 2004 and February 17 2006.

The most frequent side effects of gefitinib were acne, rash and diarrhea. Just 4 percent of patients taking the drug experienced serious adverse events – a similar rate to that seen at NCCS, where Toh estimates that “less than 5 percent” of patients on gefitinib develop side effects to the point where they have to stop therapy.

For docetaxel the most common side effects in the trial were hematological toxic effects, hair loss and weakness. Serious adverse events occurred in 18 percent of patients in this group.

The non-inferiority of gefitinib was demonstrated by the median overall survival, which was 7.7 months in patients taking the drug compared to 8 months for those taking docetaxel. One-year survival rates were 32 and 34 percent in the respective groups.

Gefitinib patients were twice as likely to have a “sustained and clinically relevant improvement in quality of life,” as measured by the Functional Assessment of Cancer Therapy-Lung score (odds ratio 1.99; P<0.0001).>

----------------

*Iressa NSCLC Trial Evaluating REsponse and Survival versus Taxotere

Wealthy elderly more susceptible to air pollution

Medical Tribune January 2009 P12

David Brill

Abandoning your condo and moving to a poorer neighborhood might be good for your health if you live in a developing country, new research suggests.

The study of 7,358 elderly residents of Chinese cities found that those who lived in the wealthiest areas were more susceptible to the damaging effects of air pollution than those living in less prosperous parts of town.

An equivalent increase in pollution levels was linked to worse cognitive function, poorer self-reported health and greater difficulties with activities of daily living among residents of the highest GDP neighborhoods compared with the lowest.

The findings are at odds with research from Western populations which has found that the poorer the neighborhood, the greater the exposure to air pollution and the worse its effects on health. [Environ Health Perspect 2003 Dec;111(16):1861-70]

The new study shows that the relationship between air pollution and health in developing economies is more complex than previously thought, one of the researchers said.

“People tend to think in developing countries that when there’s more development there should be higher pollution but that is not what we’ve found. We showed that there is no clear correlation between the economic development level and the air pollution level,” said Rongjun Sun, an associate professor of sociology at Cleveland State University, US.

“The major message of our paper is that air pollution does have a dramatic impact on the health of the elderly but it’s not as simple as people imagine. I think when we look at this we will have to take a longer-term perspective.”

The researchers used data from the third wave of the Chinese Longitudinal Health Longevity Survey, conducted in 2002. Over-65s from 735 districts in 171 cities were included in the analysis. [Am J Epidemiol 2008 Dec 1;168(11):1311-8]

The reasons for the apparent discrepancy between East and West are not clear but may reflect differences in the usage of natural resources at the different stages of economic development, suggested Sun.

History suggests that as countries develop they move from industrial economies to more service-based economies, eventually becoming richer and reaching the position where they can begin to address the quality of the environment, he added.

Managing diabetic retinopathy in primary care

Medical Tribune January 2009 P14-15

Diabetic retinopathy is a leading cause of visual loss in Asia and one of the major chronic eye diseases handled by GPs. Left untreated, it can result in permanent blindness from neovascular glaucoma or tractional retinal detachment arising from proliferative diabetic retinopathy.

The condition is expected to become more common as the prevalence of diabetes continues to rise in Asia.

A recent study found that 38.1 percent of diabetics who were referred for retinal assessment as part of a nationwide screening program in Singapore had retinopathy. [Ann Acad Med Singapore 2008 Sep;37(9):753-9] The Singapore Malay Eye Study, meanwhile, demonstrated a retinopathy prevalence of 35 percent among diabetics of Malay ethnicity, of whom 9 percent had vision-threatening retinopathy. [Ophthalmology 2008 Nov:115(11):1869-1875]. This high rate of diabetics suffering from retinopathy is consistent worldwide. The proportion of type 2 diabetics having retinopathy has been reported to be 40.3 percent in the US, 35 percent in Taiwan and 10.5 – 26.2 percent in India.

Pathogenesis

Diabetic retinopathy is a highly specific microvascular complication of both type 1 and type 2 diabetes mellitus, resulting from progressive damage to the retinal blood vessels caused by hyperglycemia in the blood. The condition is caused by increased vascular permeability at onset, leading to fluid accumulation in the retina. With time, there is vascular shutdown, causing ischemia of the retina. This leads to retinal neovascularization at the disc or elsewhere, vitreous hemorrhages, fibro-proliferative changes and retinal detachment. Neovascular glaucoma can also develop. The prevalence is strongly related to the duration of diabetes mellitus, and most diabetic patients will develop retinopathy with time.

See the sidebar for a classification of the different disease stages.

Screening

As patients with sight-threatening retinopathy may not show any symptoms, fundal screening of diabetic patients is crucial in helping to identify those at risk of developing complications that will impact on their vision and quality of life. The importance of regular screening for diabetics, therefore, cannot be understated.

All diabetic patients should be screened for retinopathy on an annual basis at the very least, beginning from the point of diagnosis. Those who are at high risk for developing retinopathy need to be monitored more closely and should be screened at least twice yearly. The major risk factors to consider are hypertension, high cholesterol, smoking, patient’s age, duration of diabetes and a history of poor glycemic control. The Singapore Malay Eye Study also found that a history of stroke, cardiovascular disease or chronic kidney disease was associated with vision-threatening retinopathy.

Female diabetics who are planning to conceive should be screened prior to conception and again in the first trimester. The regularity of follow-up should then be determined based on the results of the first trimester examination.

For patients with established retinopathy, the timing of follow up examinations depends on their disease status.

Physicians who are involved in providing diabetic care have a pivotal role in ensuring that patients are screened. This can be performed via fundal photography, indirect fundoscopy or direct ophthalmoscopy through a dilated pupil.

While the need for regular screening is well accepted by the medical community, it is an unfortunate reality that patients are often not screened as frequently as they should be. Many patients do not understand the progressive nature of the disease process, mistakenly believing that if there is nothing wrong with their vision, then they do not need to see an eye doctor. Many appointments are missed as a result, and the early signs of diabetic retinopathy can often go undetected. Accessibility can also be a problem, particularly in rural areas, and can also contribute to the missing of screening appointments.

We must educate patients on the importance of these check-ups, and help them to understand that by the time they discover they have developed visual problems, it may already be too late to treat them. GPs can also help patients to attend their screening appointments by checking regularly whether they are compliant with their schedules, reminding them about upcoming
visits and making sure that they are referred to the most appropriate and convenient center.

Practice guidelines

The most widely-used guidelines on diabetic retinopathy come from the American Academy of
Ophthalmology. These have been incorporated into clinical practice guidelines on the management of diabetic retinopathy from Singapore’s Ministry of Health, published in January 2004, which help GPs plan their management and screening schedules for their patients. Diabetic retinopathy guidelines are also available from the Academy of Medicine of Malaysia.

Treatment

Laser treatment is the major therapy for diabetic retinopathy but can lead to long-term side effects such as a reduced field of vision.

There is now a considerable weight of data showing the benefits of good glycemic control on
retinopathy outcomes. The Diabetes Control and Complications Trial (DCCT) found that an intensive strategy reduced the risk of developing retinopathy by 76 percent and slowed disease progression by 54 percent. [N Engl J Med 1993 Sep 30;329(14):977-86] Recent data from the United Kingdom Prospective Diabetes Study (UKPDS) show that the benefits of intensive glucose control extended long beyond the trial intervention, with a 24 percent risk reduction for microvascular disease noted 10 years after the conclusion of the study. [N Engl J Med 2008 Oct 9;359(15):1577-89]

Tight blood pressure control is also important. The original UKPDS data demonstrated a 47 percent reduction in the risk of having decreased vision in both eyes, after 9 years of follow up. [BMJ 1998 Sep 12;317(7160):703-13] The 2008 data showed that the benefits disappeared once treatment was withdrawn, suggesting that blood pressure control needs to be maintained in order to continue to derive the maximum benefits. [N Engl J Med 2008 Oct 9;359(15):1565-76]

Medication adherence is often a major obstacle in achieving these targets. GPs should continue to ensure that patients are well-educated on the importance of taking their drugs, making them aware that failure to do so increases their risk of retinopathy. Regular HbA1c and blood pressure tests should be carried out to monitor progress, and medication adjusted accordingly.

Disease management tools

In October 2006, the Ministry of Health in Singapore launched the Chronic Disease Management Program, focusing initially on diabetes and then on hypertension, dyslipidemia
and stroke. The plan is to transform management of these diseases by forming an effective
partnership among GPs, medical specialists and patients through effective information flow within the partnership throughout the healthcare continuum. The program aims to equip GPs with a better understanding of patients’ medical histories through up-to-date electronic records and, in turn, reduce medical costs and enable the provision of quality healthcare services customized to individual requirements.

This integrated clinic management system provides GPs with a complete system to manage their patients and clinic operations. Critical clinical indicators are stored, enabling GPs to use this data to track the progress of their patients. Clinical decision support tools are also built into the system to help GPs plan effectively and communicate care plans to their patients. In this way, schedules for retinopathy screening can be built into the patients’ management plan, helping doctors keep to the intended schedules.

Conclusion

Regular screening is the cornerstone of detecting, monitoring and managing diabetic retinopathy and should be arranged from the very point of diagnosis. Patients should be educated about the importance of screening and followed up at all stages to ensure compliance to their schedules. Good glycemic and blood pressure control are also of vital importance in preventing the development and progression of this potentially sight-threatening condition. It is strongly recommended that the organization of retinopathy screening be primarily the responsibility of the GPs, who will then refer all patients with retinopathy or media opacity to an ophthalmologist for more specialized treatment.

Online Resources:

The American Academy of Ophthalmology guidelines:

www.guideline.gov/summary/summary.aspx?doc_id=4350

Office BP not prognostic for resistant hypertension

Medical Tribune January 2009 P16
David Brill

Office-based blood pressure (BP) measurements offer “no prognostic value” for patients with resistant hypertension, a recent study has concluded.


Ambulatory BPs – both systolic and diastolic – were predictors of future cardiovascular morbidity and mortality whereas neither measurement was a significant indicator when recorded in the office, the researchers found.

The study, which followed up 556 outpatients for a median of 4.8 years, also showed that nighttime ambulatory BP was superior to daytime as a prognostic indicator, suggesting that these time periods should be analyzed seperately to give the best assessment of a patient’s cardiovascular risk.

It is only the second prospective study to assess the different BP monitoring strategies in resistant hypertensive patients, according to the researchers, who are based at the Federal University of Rio de Janeiro, Brazil. They note that the superiority of ambulatory BP “is not generally accepted,” despite several studies showing that it offers better cardiovascular risk prediction than office BP in various other patient populations. [Arch Intern Med 2008 Nov 24;168(21):2340-6]

Dr. Chai Ping, a Singapore-based specialist, said that the study should encourage physicians to use ambulatory BP more often for patients with resistant hypertension.

“In the initial evaluation of a patient with elevated office BP despite three or more medications, ambulatory BP monitoring should be performed to confirm that the BP is truly elevated and not a ‘white-coat’ effect,” he said.

“This paper also tells us that suboptimal BP control, as has been known for more than 4 decades now, confers a worse prognosis for hypertensive patients, so every effort must be made to control BP to the targets as recommended by current clinical practice guidelines,” added Chai, who is clinical director of the noninvasive cardiac laboratory at the National University Heart Centre Singapore (NUHCS).

The patients included in the study met standard criteria for resistant hypertension. The mean hypertension duration at enrollment was 18 years. Some patients were followed up for as long as 9 years.

A total of 109 patients (19.6 percent) reached the study’s primary endpoint – a composite of fatal and non-fatal cardiovascular events.

Patients with a one standard deviation increase in nighttime systolic BP at baseline had a 38 percent increased risk of reaching this endpoint following multivariate adjustment (hazard ratio [HR] 1.38), while an equivalent increase in nighttime diastolic BP yielded a 36 percent increase in risk (adjusted HR 1.36; P<0.05 for both).

The only significant predictor of death was a so-called “true” diagnosis of resistant hypertension, based on ambulatory BP monitoring rather than office-based measurement. This diagnosis was associated with a twofold increase in the risk of all-cause mortality (adjusted HR 2.00; P<0.05).

Chai estimates that up to a quarter of patients being followed up at the NUHCS have resistant hypertension. He said that he presently uses both forms of BP measurement but noted that not all hypertensive patients require ambulatory BP monitoring.

The results of the study cannot be generalized to all patients with hypertension, he added.