Stockings ineffective for DVT prevention after stroke

Medical Tribune July 2009 SFIV

David Brill

Compression stockings do not reduce the risk of deep vein thrombosis (DVT) in stroke patients, despite their widespread usage for this purpose, a major international study shows.

The multicenter CLOTS* 1 trial, involving 2,518 patients, found that stockings were not only ineffective, but increased the risk of ulcers, blisters and skin necrosis.

The results have prompted calls for revision of guidelines, as experts point to substantial cost and time savings from abandoning the practice. Some hospitals in Asia are already reviewing the findings, and may stop using stockings for stroke patients in the near future.

The trial was carried out across 64 centers in the UK, Australia and Italy. DVT occurred in 10 percent of patients who were randomized to thigh-length stockings, and 10.5 percent who were randomized to no stockings. [Lancet 2009 Jun 6;373(9679):1958-65]

All patients were immobile and had been admitted to hospital within a week of acute stroke. They were assessed for DVT at 7 to 10 days, and again at 25 to 30 days.

“In this study, we have shown conclusively that compression stockings do not work for stroke patients,” said study author Professor Martin Dennis of the University of Edinburgh, UK. “National guidelines need to be revised and we need further research to establish effective treatments in this important group of patients.

“Given that most national guidelines recommend stockings in at least some patients, the results of our study will affect the treatment of millions of patients each year. Abandoning this ineffective and sometimes uncomfortable treatment will free up significant health resources – both funding and nurse time – which might be better used to help stroke patients,” he said.

DVT is thought to be less common among Asians than Western populations, but compression stockings are nonetheless commonly used for prophylaxis in stroke patients with lower limb weakness. [Ann Acad Med Singapore 2007 Oct;36(10):815-20]

Dr. Lee Sze Haur, senior neurology consultant at the National Neuroscience Institute (NNI), Singapore, said, however, that this practice “will likely change” in light of the new data.

“Based on the CLOTS trial, there is good reason to consider discontinuing the use of graded compression stockings for prevention of DVT in patients with acute stroke, as this will save cost and time as well as reduce the incidence of skin complications,” said Lee.

National University Hospital, meanwhile, is currently reviewing the evidence before changing its use of compression stockings, according to senior neurology consultant Dr. Bernard Chan. He noted that stockings remain effective for DVT prevention in post-surgical patients, but said that the usage for stroke has been “a long-standing practice without good clinical evidence.”

Two other studies are in progress to establish alternatives for post-stroke DVT prevention. CLOTS 2 compares thigh-length and below-knee stockings, but is now expected to finish early in light of CLOTS 1. The third trial is testing the effects of intermittent pneumatic compression, and is scheduled for completion in 2013.

Blisters, ulcers, skin breaks and necrosis were reported in 64 of the 1,256 patients given stockings in CLOTS 1 (5 percent), compared to just 16 of 1,262 control patients (1 percent; odds ratio 4.18; 95 percent CI 2.40 – 7.27).

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*CLOTS: Clots In Legs Or Stockings After Stroke

Tumor compartments: A ‘revolution’ in cancer surgery

Medical Tribune July 2009 SFIV
David Brill

A novel approach to treating cervical cancer may signal the end of the radical hysterectomy and could one day revolutionize the field of surgical oncology, says a pioneering team of German surgeons.

By removing only the embryologically defined ‘compartments’ in which tumors are most likely to spread, the surgeons can spare surrounding tissues and minimize collateral damage.

The technique reduces complications and recurrence rates, removes the need for radiotherapy, and could improve survival rates by as much as 20 percent compared to conventional hysterectomy, the group reported recently in The Lancet Oncology.

Research is already underway to extend the concept to vulvar and endometrial cancers, said lead researcher Professor Michael Höckel, chairman of the department of obstetrics and gynecology at the University of Leipzig, Germany.

“We have found that the tumor is confined for a long time in its natural course to a defined tissue compartment – it’s not like an explosion infiltrating all tissues around the tumor,” said Höckel.

“This new perspective in surgical anatomy enables you to see and operate on the tissue in which the tumor is spreading, irrespective of the tumor entity. This is a general principle which could really revolutionize surgical treatment for malignant disease,” he said.

The cervical cancer procedure – total mesometrial resection (TMMR) – targets only the non-distal part of the Müllerian compartment. Surgeons remove the proximal vagina, uterus and extra-cervical mesenchyme but spare nearby non-Müllerian tissues, including the nerves which supply the vagina, bladder and rectum.

Results from 212 women who underwent TMMR without radiotherapy at the University of Leipzig show an overall 5-year survival rate of 96 percent, and recurrence-free survival of 94 percent. The study was conducted prospectively from October 1999 to July 2008 on women with early-stage cancers: International Federation of Gynecology and Obstetrics (FIGO) stages IB, IIA and selected IIB. [Lancet Oncol 2009 May 29; Epub ahead of print]

Sixty two percent of procedures were complication-free at a median of 41 months’ follow-up; 35 percent of patients had grade one complications and 9 percent had grade two. Three patients had developed pelvic cancer recurrence, five developed distant recurrences, and two developed both pelvic and distant recurrence.

Höckel and colleagues developed the principle of TMMR by studying uterovaginal development in embryos and fetuses – enabling discrimination of tissue compartments on the basis of their embryological origin. Previous work showed that early cervical tumors grow largely along these lines. [Lancet Oncol 2005 Oct;6(10):751-6]

Singapore surgeon Adjunct Associate Professor Yam Kwai Lam said that he would be “open to any new technique” as long as it provided “substantial overall benefit to the patient.”

“The published results look impressive, but lacking in long-term survival data. In order for the technique to replace conventional hysterectomies, validation would require a large randomized controlled trial to provide the answer,” said Yam, head and senior consultant in the department of gynecological oncology at KK Women’s and Children’s Hospital.

Höckel has previously presented TMMR to surgeons in Southeast Asia – performing live demonstrations in Hong Kong in December 2006, and Bangkok in August 2008.

A multicenter trial is due to launch soon in Germany, with a view to comparing results of 200 TMMRs against 200 conventional hysterectomies. Publication is expected in around 4 years, said Höckel, who has not performed a standard hysterectomy since first developing TMMR some 10 years ago.

“The conventional techniques have no right to exist any longer because they are wrong. Now that we know how a tumor is spreading … it’s no longer acceptable to use these sub-prime concepts and techniques,” he said.

Pain perception: Personality goes a long way

Medical Tribune July 2009 P12

David Brill

Personality has a major influence on the way people perceive headaches, and should be considered when assessing patients, say Italian researchers.

In a recent study they found that ‘emotionally overwhelmed’ people report a greater affective dimension to their pain than those with other personality types, yet score the same on a simple measure of pain intensity.

The other personality types – conversive, depressive and copers – did not differ significantly in their perception of pain.

The findings should encourage physicians to routinely consider a patient’s personality and emotions before simply prescribing medications, said lead researcher Professor Franco Mongini, of the Headache and Facial Pain Unit at the University of Turin.

Moreover, presentation with a headache or migraine could be a warning sign of an underlying personality disorder or mental health problem, he said, adding that early recognition could facilitate referral to a specialist before the pain gets worse.

“I keep seeing patients with chronic migraine and chronic tension-type headache together, and they have been receiving new drugs. But very often the patient’s personality and the consequences of this personality have not been considered,” said Mongini, who typically questions new patients on their history of phobias, panic attacks and sleep disturbances, among others, before considering whether to treat with cognitive behavioral therapy.

“I’m convinced after years and years of work that the approach to the problem of chronic head pain should be remodeled and widened. I’m not saying that drugs should not be prescribed – I prescribe a lot of medications myself – but other factors should be considered and treated also with non-pharmacological methods,” he said.

Mongini and colleagues assessed 317 patients with migraine and/or tension-type headache with myogenic facial pain. They performed two types of pain assessment: the verbal MacGill Pain Questionnaire (MPQ), which classifies pain in a range of dimensions, and the visual analog scale (VAS), which measures pain intensity alone. [Pain 2009 Jul;144(1-2):125-9]

Personalities, meanwhile, were classified using 10 scales of the Minnesota Multiphasic Personality Inventory (MMPI). ‘Copers’ score normally across all domains, whereas ‘depressive’ and ‘conversive’ personalities show various elevation in scores of depression, hypochondria and hysteria. The ‘emotionally overwhelmed’ personality has elevation in all three of these scores, plus one other MMPI dimension.

The affective dimension of the MPQ was significantly higher in emotionally overwhelmed than in coper (P=0.003), depressive (P=0.027) and conversive (P=0.002) people, regardless of sex, age and type of pain. VAS score did not vary significantly between groups.

Mongini and colleagues also recently reported on a successful intervention to reduce head and neck pain in the office place. A combined educational and physical program reduced the frequency of headaches by 41 percent and the use of analgesics by 50 percent, when tested in a study of 384 civil servants in Turin. [Cephalalgia 2008 May;28(5):541-52]

Breast cancer prediction and prevention could start younger

Medical Tribune July 2009 P13
David Brill

Risk assessment for breast cancer could one day start in girls as young as 15, according to a recent paper which may open up new opportunities for early disease prevention.

Canadian researchers found that breast tissue composition – a known risk factor in middle age and above – begins to vary at a much younger age, and could provide a quantifiable way to predict risk.

It is the first extensive study to look at breast tissue composition in young women, say the authors, who used MRI in order to avoid the radiation exposure of mammography.

Percent breast water was found to decrease with age (P=0.04) – a finding which could explain why breast tissue is thought to be most susceptible to carcinogens at a young age.

The researchers also found strong correlations to height and weight – suggesting that breast composition could be influenced by factors relating to growth and development. Percent breast water was also strongly linked to mammographic density in the subjects’ mothers – lending support to a hereditary component to breast formation.

“What [this study] suggests is that prevention is going to be most effective if started earlier in life, and that measurement of breast tissue characteristics might be one way of modifying and monitoring prevention,” said lead author Professor Norman Boyd, of the Campbell Family institute for Breast Cancer Research, Toronto, Canada.

Further research is needed before risk assessment could be practiced routinely in young girls, said Boyd, noting two key areas of uncertainty. First would be to establish the most appropriate method for assessing breast composition in young women, and second would be to be determine which interventions would be appropriate and safe in those found to be at high risk.

“The long-term vision would be that we would have a method of assessing breast tissue composition as soon as the breast forms, essentially. MRI is what we’ve used, but MRI is clearly not the answer to this because it’s so expensive and there are so few machines,” he said.

“It’s difficult to know how technology is going to advance but at the moment, ultrasound looks very appealing. It can be done quickly, it can be done quantitatively, it can give us measurements of tissue volumes, which mammography does not do, it can be done very, very quickly… and it’s completely free of risk.”

Boyd and colleagues measured levels of water and fat in the breasts of 400 women aged 15 to 30, and their mothers. The percentage of water on MRI correlated strongly with mammographic density in a randomly selected subset of 100 of the mothers (r=0.85). [Lancet Oncol 2009 Apr 29; Epub ahead of print]

Height, weight and maternal mammographic density were all strongly associated with per cent breast water in young women (P<0.0001). Height and weight also correlated strongly to total breast fat, and maternal mammographic density correlated strongly to total breast water (P<0.0001).

The association between weight and percent breast water was inverse – suggesting that heavier young women are at lower risk of breast cancer. Previous studies have also shown similar findings but the mechanisms for the association remain unclear, said Boyd. The authors did, however, report an association between percent breast water and serum levels of growth hormone – a finding which could underlie the associations with height and weight, they say.

Further research is already ongoing to better understand the genetic factors that influence breast composition, added Boyd.

Dieticians call for action on overweight mothers-to-be

Medical Tribune July 2009 P16

David Brill

Overweight women should receive nutrition counseling before, during and after pregnancy, leading US dietitians have advised.

With the global obesity epidemic showing no signs of slowdown, the health of mothers and babies alike is at risk unless eating habits improve, cautions a recent joint statement from the American Dietetic Association (ADA) and the American Society of Nutrition (ASN).

Studies show that obese mothers are more likely to experience preeclampsia, gestational diabetes mellitus (GDM), gestational hypertension, postpartum anemia and cesarean delivery than women of normal weight. Their offspring, meanwhile, face an increased risk of birth defects, fetal macrosomia, childhood obesity and even perinatal death.

Ms. Ximena Jimenez, a consultant dietitian and national ADA spokesperson, said that healthcare professionals across the spectrum should work together to promote healthy eating and physical activity in women who are pregnant or planning to conceive. Physicians, for example, can play “a big role” in reinforcing the advice given by dietitians and other specialists, she said.

“A lot of the time it takes more than one type of counseling to get these women to change their lifestyle. I would encourage any healthcare professional to encourage these women to seek nutrition counseling,” she said.

“The principles are that you want them to increase whole grains and decrease refined carbohydrates like cakes, pastries and white breads. We also want them to replace saturated fat with healthy fats like omega-3 fats or fats from olive oil, canola oil or avocado, and also to increase their intake of fruits and vegetables. We also want them to be physically active,” she added.

Some 52 percent of women aged 20 to 39 in the US are overweight or obese (BMI 25 or above), according to data from the National Health and Nutrition Examination Survey of 2003-2004. Twenty-nine percent are obese (BMI 30 or above) and 8 percent are extremely obese (BMI 40 or above). Among adolescent girls aged 12 to 19, almost 32 percent are overweight or at risk of being overweight. [JAMA 2006 Apr 5;295(13):1549-55]

Despite the scale of the task, Jimenez remains optimistic that overweight women can be successfully counseled.

“I think it’s a very realistic target. There has to be promotion of healthy eating among women,” she said. “Imagine the benefits. As a society we are all going to benefit because we are going to have healthy women and healthy children.”

Jimenez highlighted studies showing the success of dietary interventions in overweight mothers, such as the Nurses’ Health Study, which found that risk of GDM was approximately halved by following a low-glycemic, high-cereal fiber diet. [Diabetes Care 2006 Oct;29(10):2223-30] The risk of preeclampsia can also be halved by taking calcium supplements, a meta-analysis of 12 studies shows. [Cochrane Database Syst Rev 2006 Jul 19;3:CD001059]

The new ADA / ASN position statement also reviews the literature on the prevalence of various pregnancy outcomes for overweight mothers and their babies. [J Am Diet Assoc 2009 May;109(5):918-27]

The risk of developing GDM, for example, is reported to double in overweight women, and increase over eightfold in the extremely obese. [Diabetes Care 2007 Aug;30(8):2070-6] Preeclampsia risk is around three times higher in pregnant women who are obese than those of normal weight. [Obstet Gynecol 2007 Feb;109:419-33]

The offspring of obese mothers are around twice as likely to have neural tube defects such as spina bifida, according to the US National Birth Defects Prevention Study. [Arch Pediatr Adolesc Med 2007 Aug;161(8):745-50] Oral clefts, hydrocephaly and cardiac abnormalities were also found to be more common in these infants than those born to normal-weight mothers.

Stroke prevention under-used in the elderly

Medical Tribune June 2009 P1&6
David Brill

Elderly patients are missing out on life-saving stroke prevention drugs in primary care, according to a report in the British Medical Journal.

Stroke patients aged 80 to 89 were almost half as likely to be receiving secondary prevention treatments as those aged 50 to 59, the researchers found.

This discrepancy in treatment was not justified by outcomes, however – receipt of the drugs halved mortality risk, regardless of age.

The study of 12,380 patients took place in England but carries an important message for Singapore, according to stroke expert Associate Professor Lee Kim En, senior consultant and head of the department of neurology at the National Neuroscience Institute, Singapore.

“We do not have local figures, but similar findings are expected in Singapore. This is a timely article serving as a reminder that social support must include ensuring the elderly receive their medications,” he said.

“As doctors, we have a responsibility to motivate our elderly patients to continue with treatment regardless of challenges, constraints and limitations. All primary care physicians must share this responsibility.”

The researchers reviewed data from 113 general practices to identify over-50s who had a stroke between 1995 and 2005 and survived the first 30 days. Therapy had to be initiated within 90 days of the stroke to be included in the study as secondary prevention. [BMJ 2009 Apr 16;338:b1279]

Overall treatment rates were low: 25.6 percent of men and 20.8 percent of women were receiving secondary prevention. Mortality within one year of stroke was 5.7 percent for patients receiving treatment, compared to 11.1 percent among those receiving no such therapy.

Treatment rates did not vary by socioeconomic status but dropped markedly with age – from 26.4 percent of patients aged 50 to 59, to 15.6 percent of those aged 80 to 89. Just 4.2 percent of over-90s were receiving treatment.

Lipid lowering drugs were particularly under-used in the elderly – the odds ratio for receipt of these therapies was 0.44 for 80 to 89 year-olds, compared with 50 to 59 year-olds (95 percent CI, 0.33 to 0.59; P<0.001).

The study did not explore the reasons for the observed age bias, but lead researcher Professor Rosalind Raine speculated that responsibility could lie with both patients and prescribers.

“We can’t leave an attack of clinical bias on the doors of the clinicians until we’ve really excluded all of the other explanations,” said Raine, professor of health care evaluation at University College London. “Patients are increasingly more informed, and so there is also a balance about what they’re asking for.”

Some experts have suggested that GPs may be unsure about the efficacy of secondary prevention drugs in the elderly since they are often excluded from clinical trials, she said. She noted, however, that there is a growing body of evidence – particularly from meta-analyses – to support the benefits of this practice. The mortality findings from the present study further underscore this point in a real-world, general practice population, she added.

Raine also ruled out the possibility that prescribers may be worried about adherence in the elderly, since the discrepancy was only evident for lipid lowering drugs and not for cheaper therapies such as antihypertensive and antithrombotic drugs. She expressed her concern that it could be the relative cost of the drugs which is driving this particular effect.

“It does make you wonder if lay beliefs about values of people in society are actually being transposed into the clinical situation. But I do not have evidence on which to base that – it’s only by exclusion of some of the other likely explanations,” she said.

Rifts widen in prostate screening debate

Medical Tribune June 2009 P1&9
David Brill

American and European experts have diverged in their stances on prostate cancer screening, as debate intensifies over the benefits of prostate-specific antigen (PSA) testing.

The subject has held center stage since the publication of two major studies in March: one showed that PSA testing every 4 years reduced mortality by 20 percent but carried a high risk of overdiagnosis; the other showed that annual screening had no impact on death rates.

The American Urological Association (AUA) has since aligned itself with the first study – recommending PSA testing in all well-informed men, and lowering the age for a first test from 50 to 40. It has also adjusted its criteria for proceeding to biopsy.

The European Association of Urology (EAU), meanwhile, has advised against population screening until more data are available – warning of the dangers of overtreatment and calling for urgent development of new diagnostic markers and screening algorithms.

Singapore experts are taking a similar stance to their European counterparts, although they note that the lower incidence of prostate cancer in Asia makes screening less worthwhile than in Western populations.

The Singapore Urological Association (SUA) nonetheless intends to downplay the role of PSA screening in this year’s upcoming Prostate Awareness Month, according to Professor Kesavan Esuvaranathan, SUA president and senior consultant, department of urology, National University Hospital.

“I wouldn’t be in a hurry to recommend screening. We don’t know for sure whether there is a benefit,” he said.

“My feeling is that it’s too early to say that PSA screening is inappropriate, but I also think that it is probably wrong to unconditionally recommend PSA screening. I think we have to wait for the long-term results of these studies.”

Associate Professor Weber Lau, senior consultant, department of urology, Singapore General Hospital, also urged caution in the use of PSA testing, stressing the need to select the right patients.

“We are quite clear that screening is not a goal for Singapore at this juncture. For people who are asking to be tested, the key words are risk stratification,” he said.

“PSA can be used as a tool for early detection of prostate cancer in the right patients. But on the other hand it can be harmful too if used in health screening without understanding the risks of the patient group and the general health of the patient.”

The 20 percent mortality reduction with PSA screening was reported in the European Randomized Study of Screening for Prostate Cancer, which included 162,387 men aged 55 to 69 from seven countries. They were assigned to PSA screening every 4 years on average, or to no screening. [N Engl J Med 2009 Mar 26;360(13):1320-8]

After a median of 9 years’ follow-up, the adjusted rate ratio for prostate cancer death in the screening group was 0.80, as compared to the control group (95 percent CI, 0.65 – 0.98; P=0.04). The absolute risk difference was 0.71 deaths per 1,000 men – meaning that to prevent one death from prostate cancer, 1,410 men would need to be screened and an additional 48 cases would need to be treated.

The second study – the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial – included 76,693 men aged 55 to 74, recruited at 10 US centers. Men were randomized to annual screening – with PSA for 6 years and digital rectal exam for 4 years – or to the control group. [N Engl J Med 2009 Mar 26;360(13):1310-9]

After 7 years’ follow-up, there were 50 prostate cancer deaths in the screening group and 44 in the control group (rate ratio 1.13; 95 percent CI, 0.75 – 1.70). Ten-year data showed similar patterns but follow-up was only complete for 67 percent of patients at the time of publication.

Despite the lack of national recommendations, PSA tests are commonly offered in Singapore as part of executive health screens, according to Kesavan. This situation need not change in light of the studies, he said, but he emphasized the importance of explaining the potential consequences before testing.

“It would place the patient in a quandary if it was not explained properly and then he had an abnormal test. Then to put that worry to rest it would require him to undergo a biopsy.”