Fears allayed over menopausal memory loss

Medical Tribune August 2009 P8

David Brill

Women who experience memory loss as they approach the menopause can be reassured that the problem is only temporary, say US researchers.

In a recent study of over 2,000 women, they found that verbal memory and processing speed appear to drop during perimenopause, but typically return to normal upon reaching postmenopause.

The findings confirm a problem which is reported by up to 60 percent of women but has been addressed by very few quantitative studies, say the authors. [Neurology 2009;72:1850-7]

Lead author of the Study of Women’s Health Across the Nation (SWAN) report, Dr. Gail Greendale, said that physicians can now use the findings to reassure concerned women and “validate their experience.”

“Women who are experiencing memory difficulties during the menopause transition often find this experience frightening. They do not know what to expect and worry that their memory will worsen over time,” said Greendale, of the David Geffen School of Medicine at the University of California, Los Angeles, US.

“The SWAN results provide women with a frame of reference … and show that the memory problems are temporary. Also, if women are having memory problems of a greater degree than that which we observed, then their physician should not ascribe the problem to menopause and should dig deeper,” she said.

The SWAN study involved 2,362 women with a mean age of 45.9. They were classified as premenopausal, perimenopausal or postmenopausal, and followed for 4 years with regular testing in domains of processing speed, verbal memory and working memory.

The decline in cognition over the menopause transition was particularly marked for processing speed: pre- and postmenopausal women showed significant improvements with repeated testing, whereas late perimenopausal women scored worse over time. A similar effect was seen for verbal memory, but there was no difference in working memory between groups.

The paper also points to cognitive benefits of early initiation of hormone therapy: women who had already begun therapy before their final menstruation scored 4 to 6 percent higher on tests than those with no prior therapy.

Estrogen has a range of effects on the brain and is thought to influence mood, higher cognitive function and motor skills. Estrogen receptor density is particularly high in the prefrontal cortex and hippocampus – hence it has been postulated that the fluctuation in estrogen levels during perimenopause could adversely influence brain function. [J Appl Physiol 2001;91:2785-801]

Only two previous longitudinal studies however have measured cognitive performance over the menopause transition, according to Greendale and colleagues. The more recent of the two, a study of 694 women from a rural community in Taiwan, found that verbal memory declined during the menopause transition. The other study found no cognitive effects of the transition on working memory or perceptual speed. [Maturitas 2006;53:447-53; Neurology 2003;61:801-6]

Knee replacements cost-effective, say US researchers

Medical Tribune August 2009 SFI
David Brill

Total knee arthroplasty (TKA) is cost-effective, especially when performed in high-volume centers, according to a US study.

The findings will prove valuable for informing both policy and practice as the number of TKAs performed each year continues to spiral upward, the authors say. Some 500,000 TKAs were performed in the US in 2005, at a cost of over US$11 billion, and the number of procedures is projected to reach 3.5 million by 2030.

The study found that the incremental cost-effectiveness ratio of TKA was US$18,300 per quality-adjusted life year (QALY) – a figure that meets most commonly used definitions of cost-effectiveness. The UK National Institute for Health and Clinical Excellence, for example, sets its cost-effectiveness threshold between £20,000 and £30,000 (around US$33,000 to US$49,000) per QALY.

The researchers, led by Dr. Elena Losina of the Brigham and Women’s Hospital, Boston, developed a computer model using Medicare claims data and outcomes data of people with end-stage knee osteoarthritis. [Arch Intern Med 2009 Jun 22;169(12):1113-21]

Quality-adjusted life expectancy increased from 6.8 to 8.0 QALYs in people who underwent TKA. Procedures performed at low-volume centers cost more and were less effective than in high-volume centers, regardless of whether patients were at high or low risk.

TKA is widely accepted as an effective procedure but assessing cost-effectiveness has proven difficult, due in part to the ethical and logistical constraints that prohibit a randomized controlled trial.

Despite the insights from the new study, however, policymakers still face many difficulties in evaluating established medical technologies such as TKA, according to an accompanying editorial by Assistant Professor Stephen Lyman, director of the epidemiology and biostatistics core at Weill Cornell Medical College, New York, and colleagues.

“At least in the US, even well-performed cost-effectiveness analyses do not influence either payers or physicians directly. Payers do not use the results to make coverage determinations nor do physicians use them to make treatment decisions. How we move from this current state to a system in which cost-effectiveness of procedures affects medical practice is unclear,” they wrote. [Arch Intern Med 2009 Jun 22;169(12):1102-3]

Demand for TKAs is also expected to rise in parts of Asia, where populations are ageing rapidly. An analysis of 1,663 procedures from a high-volume center in Singapore found that patients were typically Chinese females in their mid-60s. Ninety six percent had osteoarthritis and four percent had rheumatoid arthritis. [Ann Acad Med Singapore 2008 Nov;37(11):924-8]

Average length of stay decreased between 2000 and 2005 – due, in part, to an increase in the number of same-day admissions. Overall complication rates were 2 percent and mortality less than 1 percent, the group from Tan Tock Seng Hospital reported.

Questions raised over childhood antibiotics

Medical Tribune August 2009 SFV

David Brill

Using antibiotics to treat acute otitis media (AOM) in young children could increase their risk of recurrent infection, a recent study suggests.

Children who received amoxicillin for AOM were 2.5 times more likely to have a recurrent episode within the following 3.5 years, reported Dutch researchers, who are calling for more conservative use of antibiotics in this setting.

Senior author Dr. Maroeska Rovers said that up to 80 percent of children with mild, uncomplicated AOM will recover spontaneously, and that a 2 to 3 day “wait and see” policy is justified in such cases. Close observation by parents is required, since acute mastoiditis can result if AOM worsens and goes untreated, she said.

The British Medical Journal study included follow-up surveys from 168 children who had presented to Dutch GPs with AOM between the ages of 6 months and 2 years, and been randomized to amoxicillin or placebo. It is one of the first studies to look at the long-term effects of antibiotics in pediatric AOM, the authors say. [2009 Jun 30;338:b2525]

Sixty three percent of antibiotic-treated children had an AOM recurrence, compared to 43 percent of placebo-treated children (risk difference 20 percent; 95% CI 5-35%). Antibiotic-treated children were, however, less likely to undergo ear, nose and throat (ENT) surgery (21 percent versus 30 percent; risk difference 9 percent; 95% CI 4-23%).

Singapore expert Associate Professor Lynne Lim cautioned that more research is needed before practice should be changed, particularly given the small size of the study, the width of the reported confidence intervals and the different ethnicity and geographical location of patients.

“The debate on antibiotics use in AOM is continuing worldwide. It is definitely important to use antibiotics judiciously to avoid bacterial resistance and worse outcomes, if any, but until we are able to comcommitantly answer in the same study the complication rates and other problems associated with no antibiotic use, we cannot answer the question fully,” said Lim, head of the pediatric ENT service and senior consultant ENT surgeon at the National University Health System Singapore.

“The study suggests that more large, population-based, randomized clinical trials should be done to determine the cost-benefit of antibiotic use in AOM. I will continue treating as normal until more data are out,” she said, adding that that she typically follows US guidelines when treating AOM, and prescribes high-dose oral amoxicillin or amoxicillin/clavulanate potassium (80-90 mg/kg per day) for 7 to 10 days for children under 2.

Rovers, a clinical epidemiologist at University Medical Center Utrecht in the Netherlands, stressed that the “wait and see” policy should only apply to mild, unilateral AOM. Children under 2 years who have bilateral AOM or AOM with otorrhea should receive antibiotics without delay, she said, citing a meta-analysis of 1,643 children which found that antibiotics were of greatest benefit in these subgroups. [Lancet 2006 Oct 21;368(9545):1429-35]

“We now know which children benefit most from antibiotics but we also know that there is some harm. The next step for me will be to try to study the benefit and risk. Then we can say whether the guidelines should be changed or should not be changed,” she said.

Rovers and Lim both added that analgesics should be given to all children with AOM, regardless of whether antibiotics are prescribed.

NHG ups ante on manpower training budget

Medical Tribune August 2009 SFIX
David Brill

The National Healthcare Group (NHG) is to invest an additional $1.3 million in training fellowships this year, the group’s chairman announced recently.

The funding boost will see 189 staff undergo specialist placements through the Health Manpower Development Plan (HMDP) awards – up from 138 recipients last year.

This year’s awardees comprise 75 doctors, 77 nurses, 23 health sciences professionals and 14 healthcare administrators.

“With the bar for healthcare being raised consistently, we need to relentlessly improve our healthcare delivery, to become the preferred healthcare provider in Singapore and the region. HMDP is, and will continue to be, one of the key anchors for NHG’s staff training and development efforts,” said NHG Chairman Madam Kay Kuok, who presented the awards in a ceremony at the Institute of Mental Health (IMH).

Recipients of the HMDP award undergo training fellowships – often overseas – in skills and specialist areas which are not easily found in Singapore. The focus of this year’s awards is on health services and outcomes research, multi-disciplinary training, the ageing population and mass disasters and emergencies.

Previous winners “have done us proud,” said Kuok, highlighting the example of Dr. Sung Min, consultant in the department of child and adolescent psychiatry at IMH. Sung established Singapore’s first public autism clinic at IMH in April 2006, having spent a month studying in the UK as part of her HMDP award the previous year. The clinic has now seen more than 650 patients.

The total budget for this year’s awards is S$5.7 million – co-funded by NHG and the Ministry of Health (MOH).

The HMDP was launched in 1980 by MOH, but administration has since been devolved to NHG and SingHealth.

The unsung heroes of healthcare: Part I

Medical Tribune August 2009 SFXII

David Brill

Born in 2004 from the legacy of SARS, the annual Healthcare Humanity Awards are given to those who go above and beyond the call of duty to improve the care and wellbeing of patients. David Brill spoke to two of this year’s recipients about their achievements, challenges and hopes for the future.

The children’s champion: Ensuring a bright future for Singapore

Some doctors continue their medical education by reading journals and taking exams. Others brush up by attending conferences or participating in workshops.

Dr. Ong Say How is different. He keeps up to date by watching cartoons and listening to pop music. Unlikely sources of information for most specialists, but an important part of the routine for this dedicated child and adolescent psychiatrist. Following popular culture helps him better relate to his patients, he says. And few would question his approach: in 2005, Ong received the Best Psychiatrist Award from the prestigious Columbia University in New York, US, for his volunteer work in Caring@Columbia – a program for underprivileged and at-risk children. Other accolades have followed since returning to Singapore, culminating in his recent Healthcare Humanity Award.

Engaging troubled children would be a daunting task for most, but Ong is completely relaxed around youngsters. This, he says, is his strength – allowing him to break down the formality of a clinic setting using humor, anecdotes and roleplays. “I think like a kid sometimes, so we can talk on the same page and be on the same wavelength. Most of the time when kids come to me they have already seen their teachers, seen their school counselors, talked at length with their parents, and nothing has helped. So I have to take a different approach to get them to confide in me,” he says.

As a consultant and deputy head of child and adolescent psychiatry at the Institute of Mental Health, Ong has spent much of his career engaging with the youth of Singapore. He also runs an outpatient clinic at the Child Guidance Clinic and is involved with various workgroups and committees, including the national Pediatrics Services Review Committee. His caseload is wide and varied, but most commonly involves anxiety, depression, stress-related conditions and attention deficit hyperactivity disorder.

Progress has been made but child psychiatry remains a “high-need medical area” for Singapore, he says. Surveys point to a fairly high number of undiagnosed psychiatric disorders among schoolchildren, suggesting that screening is one of the areas in need of strengthening. Improving step-down facilities and access to treatment in the community are also amongst the most pressing challenges, he says.

“Some kids fall through the gaps because they are not very aware of the services available to them, or sometimes still face a stigma about seeking psychiatric help. And parents alike … a lot of families are still stricken with fear when it comes to seeking help for their mental health. Rather they will bring the kids to see a non-professional, or a temple medium or a traditional healer, and in the end they suffer.

“Recently I lost a kid because the parents were not keen to bring the child forward and refused to seek help in the community setting. Someone so young and intelligent and with so many good things going for him – it’s just sad that the parents or the child himself refused to seek proper help.”

Despite the tragic stories such as this, Ong remains upbeat about the future of Singapore’s youth. New outreach programs are underway in schools, bringing psychiatrists closer to counselors and teachers, and opening up new avenues for screening and prevention. Mental wellbeing, Ong hopes, will one day be entrenched in the national curriculum. In the meantime he will continue to champion for the children through his tireless work in the clinics and community.

“Seeing them open up and let you into their thoughts and feelings is the first step to building that rapport and to making the first change. It’s very rewarding when they start to trust me that I will help see them through and see them smile again. The children are our future, and in order to secure a future for Singapore we must make sure that they are well taken care of,” he says.

The Unsung Heroes of Healthcare: Part II

Medical Tribune August 2009 SFXII
David Brill

Born in 2004 from the legacy of SARS, the annual Healthcare Humanity Awards are given to those who go above and beyond the call of duty to improve the care and wellbeing of patients. David Brill spoke to two of this year’s recipients about their achievements, challenges and hopes for the future.

A picture of health: Putting patients at the center

Associate Professor Chia Sing Joo is designing a hospital. It’s his biggest project to date, yet he works on it alone. There are no meetings, no paperwork and no phone calls – he’s been doing it for years and no one even knows about it.

The blueprints, for now at least, are in Chia’s mind. He refines them constantly, hoping one day for the opportunity to put them to use. “I would like to build a hospital which is totally patient-focused,” he explains. “Patients don’t have to wait for a long time, and they don’t have to worry about unforeseen outcomes because the process is so transparent. The doctors all share the same values and are not for profit. Every patient would want to come here, and every doctor would want to train here.”

This vision may sound ambitious, but Chia is already striding toward it. As chairman of the division of surgery at Tan Tock Seng Hospital (TTSH), Singapore, he has worked hard to improve processes of care and ensure that the welfare of patients remains the primary focus. Day surgery is up; unnecessary inpatient stays are down. Increased collaboration with GPs has freed up hospital beds and reduced waiting times, and the establishment of a multidisciplinary surgical oncology group has improved quality of care and outcomes for cancer patients. The list goes on, and many more projects lurk in the pipeline.

Communication is a theme that surfaces repeatedly in conversation with Chia, and would form a central pillar in the ethos of his patient-centric hospital. As a member of TTSH’s mediator team he is often on the front line against complaints, and has come to believe that the majority could be avoided simply by spending more time talking to patients and their relatives. Misinformation can lead to misunderstandings, and anxiety and stress typically follow, he says. And nowhere is this need for openness greater than when advising patients on surgery.

“First I explain the options to the patient and the complications of each,” says Chia, who is also a senior consultant urologist. “Second, I tell them what I would choose if they were my uncle or auntie. Finally, I let them know that there is no guaranteed surgery in this world. Expectations are important – patients have to understand that we are only human and a lot of things are beyond our control. If you do these things, there are very few patients who will not trust you. If complications arise, 99 percent will understand that you have done your best and this was something unavoidable and unpredictable.”

Chia’s quest to improve patient-doctor communication, however, does not end in the clinic or the operating theatre. He speaks in public forums, has recently published a book entitled Male Urological Problems: The Essential Guide for Every Man & Couple, and is now working on another layman-orientated book about “how to spice up your sex life”. He also gives out his home and hand phone numbers to patients, and encourages them to call if they have any concerns or questions. And, it seems, they don’t hesitate: he estimates that his phone rings every 5 or 6 minutes on a typical working day.

Even by doctors’ standards, Chia is a busy man. In between the phone calls, books and surgery, he also spends one day a week as a visiting consultant at KK Women’s and Children’s Hospital, works on several research papers, oversees the development of a new training center at TTSH, raises three sons – none of whom want to be doctors – and still finds the time to run for an hour before dinner. Citing “every day” as his career highlight, however, it is clear that he wouldn’t change a thing. Except, of course, for the long-awaited chance to roll out those imaginary blueprints. “If I really had the opportunity to build my own hospital, that would be a great challenge for me,” he says.

Urine test could allow for lung cancer risk prediction

Medical Tribune August 2009 P12
David Brill

A simple urine test could one day reveal which smokers are at greatest risk of developing lung cancer, according to a team of Singaporean, Chinese and American scientists.

The group recently reported the first link between elevation of certain urinary metabolites – total NNAL* – and increased lung cancer risk in humans. Cigarette smokers with the highest total NNAL levels were over twice as likely to develop lung cancer.

A commercially available test remains at least 5 years off, but the identification of these urinary biomarkers raises “an exciting possibility,” say the researchers.

“Such a test would enable doctors to screen more frequently for lung cancer in smokers with high levels of biomarkers, and provide a strong incentive for these smokers to quit smoking,” said study authors Associate Professor Yuan Jian-Min of the University of Minnesota, US, and Associate Professor Koh Woon-Puay of the National University of Singapore, in a joint statement to Medical Tribune.

“With the identification of new biomarkers, we could ultimately develop an assay that simultaneously quantifies a panel of tobacco carcinogens or their metabolites to best predict the risk of lung cancer for an individual smoker,” they said.

The work goes some way towards explaining why some smokers develop lung cancer while others do not. With over 60 established carcinogens in cigarette smoke, it may be that individual differences in the uptake and metabolism of particular chemicals play an important role in the development of cancer, the authors say.

One such carcinogen, NNK**, has been strongly linked to lung cancer but an epidemiological link had only been shown in animal studies.

Yuan, Koh and colleagues instead investigated levels of NNAL – a metabolite of NNK – in a nested case-control study using data on 63,257 men and women from the Singapore Chinese Health Study, and 18,244 men from the Shanghai Cohort Study. They identified 246 cases of incident lung cancer, and 245 matched controls. [Cancer Res 2009;69:2990-5]

The odds ratio of developing lung cancer was 2.11 for smokers who were in the highest tertile of urinary total NNAL before cancer diagnosis, compared to those in the lowest tertile (95% CI 1.25 – 3.54; P for trend = 0.005).

Combination with cotinine, a nicotine metabolite, further increased the predictive value of NNAL: the odds ratio for developing cancer was 8.47 for smokers in the highest tertile for both markers, compared to those in the lowest tertile (95% CI 3.69 – 19.46; P for trend – 0.005).

“Biomarkers for prediction of cancer risk are useful as proxy measures of outcome in interventional studies. Nevertheless, for smokers, the best intervention for the reduction of lung cancer risk is still to quit smoking,” added Yuan and Koh.

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* NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Total NNAL is the sum of NNAL and its glucuronides.
**NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

New CV risk score could replace Framingham in UK

Medical Tribune August 2009 P13

David Brill

The long-established rules for cardiovascular risk assessment could be overhauled in the UK, following calls for the Framingham risk score to be abandoned in favor of a newer model.

An independent analysis found the QRISK score to be superior to Framingham on all measures – identifying a higher proportion of people who went on to develop cardiovascular disease.

The findings prompted a resounding endorsement of QRISK in a British Medical Journal editorial, recommending its routine adoption. Reports have since emerged that QRISK is under review at the UK National Institute for Health and Clinical Excellence (NICE), and is set to be integrated into software packages used by GPs.

University of Oxford statisticians validated QRISK using an independent cohort of 1.07 million patients from 274 UK general practices. There were 43,990 cardiovascular events over a median of 4.9 years’ follow-up. [BMJ 2009 Jul 7;339:b2584]

QRISK under-predicted cardiovascular risk by 12 percent (13 percent for men and 10 percent for women) but was considerably more accurate than the Anderson Framingham algorithm, which overestimated risk by 23 percent (32 percent for men and 10 percent for women).

“We believe this formula has the potential to save many thousands of lives, by helping clinicians to more accurately predict those at risk of developing cardiovascular disease – the nation’s biggest killer,” said Professor Julia Hippisley-Cox of the University of Nottingham, who led the team which developed the QRISK score.

“It will arm doctors with all the information they need to decide how best to target patients with preventative measures such as lifestyle advice and cholesterol-lowering treatments. We are delighted to receive another strong endorsement of the value of QRISK in assessing the risk of heart disease in the UK population,” she said.

QRISK includes most of the traditional risk factors seen in the Framingham equations but also includes family history, social deprivation, body mass index and use of antihypertensive treatments. It was first developed and validated in 2007, using data from 1.28 million patients from 318 UK general practices. [BMJ 2007 Jul 21;335(7611):136]

Further refinements to the model – QRISK2 – were published last year to include ethnicity and other conditions such as type 2 diabetes, hypertension, atrial fibrillation, renal disease and rheumatoid arthritis. The updated version, however, has yet to receive independent validation. [BMJ 2008 Jun 28;336(7659):1475-82]

The external validation of the original QRISK was commissioned by the UK Department of Health to compare the model against the Anderson Framingham algorithm, which is presently recommended by NICE as the basis for deciding on whether to prescribe statins.

The incidence rate of cardiovascular events was 30.5 per 1,000 person years among men who were classed as high risk by QRISK, compared to 23.7 per 1,000 person years among men classed as high risk by the Anderson Framingham score. In high-risk women, the incidence rates were 26.7 per 1,000 person years for those identified with QRISK, and 22.2 per 1,000 person years for those identified by Anderson Framingham.

Despite the improvements with QRISK, the data provide “a sobering message about the current state of cardiovascular risk prediction,” according to the authors of the accompanying editorial. Increased usage, improved data collection and further refinements to the system could however increase the accuracy of risk prediction in future, wrote Professor Rod Jackson of the University of Auckland, New Zealand, and colleagues. [BMJ 2009 Jul 7;339:b2673]