Costs of allergy exceed TB & AIDS

The World Allergy Organisation (WAO) has published its first report – The State of World Allergy Report – on the extent of allergy and chronic respiratory diseases worldwide. The WAO called for immediate collaboration to tackle the current escalation in allergy cases.

In the last 20-30 years, the prevalence of allergic diseases has increased significantly – a trend that shows no signs of abating. It is estimated that 400 million people worldwide experience allergic rhinitis and 300 million people worldwide have asthma with estimated economic costs exceeding those of tuberculosis and HIV/AIDS combined.

One of the most alarming findings from the report is that while the incidence of allergy and associated diseases has increased significantly, the number of healthcare professionals trained in the diagnosis and treatment of allergy has decreased, leaving many patients undiagnosed and untreated. The report is a first step in addressing this issue.

● The report can be downloaded here:
www.allergysa.org/pdfs/world-allergy-report-2008.pdf



Research suggests SVDP better way to measure amniotic fluid

Women often undergo early caesareans or induced labour following detection of decreased amniotic fluid volume, because this is seen as a sign of foetal distress. While no gold standard exists for measuring amniotic volumes, a new Cochrane Systematic Review suggests that the single deepest vertical pocket (SDVP) technique is better than the commonly used amniotic fluid index (AFI) method.

Amniotic fluid protects unborn babies from trauma and infection. A decreased volume may indicate that a pregnancy is at risk. If doctors detect low volumes they often recommend an early delivery. Both AFI and SDVP are assessed using ultrasonography. The AFI is calculated by adding the depths at four different pockets in the amniotic cavity, whereas the SDVP method measures the single deepest pocket.

A team of Cochrane researchers reviewed data from four trials that together involved 3,125 women. They found that when AFI is used more pregnant women are diagnosed with low fluid volumes than occurs when SDVP is used. There is, however, no indication that AFI is doing a better job of detecting distressed foetuses. As a result, when AFI is used more women will be encouraged to have early deliveries and more women will have a caesarean delivery for socalled ‘foetal distress’ than are needed than if SDVP was used.

“The problem is having a method that detects foetuses that are in trouble, without including many others that would happily go to term and have a spontaneous onset of delivery, and at the moment it seems that SDVP is the best available option when it comes to measuring amniotic fluid volume,” says Asfraf Nabhan, who led the research at the Ain Shams University in Cairo, Egypt.



Inflammatory Bowel Disease also found in infants – study

Inflammatory Bowel Disease (IBD) – a condition that includes both Crohn’s Disease and Ulcerative Colitis – is no longer limited to the adult population. Research carried out by the Pediatric Clinic of the University of Trieste, Italy, at the Institute for Maternal and Child Health Burlo Garofolo, a hospital highly specialised in infant health, reports an increased prevalence of IBD not only among the general paediatric population, but surprisingly, also in children younger than two years of age. The study, launched in 1984 and completed over 20 years, was recently published by the European Journal of Pediatrics. It reached two main conclusions:

■ very early onset IBDs (before the age of 2) represent an estimated 9% of all the paediatric onset IBDs (occurring before the age of 16)

■ these early forms are particularly severe versions of the disease and may hide an underlying inborn error of the immune system, therefore they require a more invasive therapy other than surgical and immunosuppressive therapies.  Moreover, since the disorder may initially be mistaken as a food allergy, the diagnosis is often delayed.

● IBD and IBD mimicking enterocolitis in children younger than 2 years of age – Z. Cannioto, et al – European Journal of Pediatrics.



Family history not good predictor of breast cancer

A study published recently in the open access journal BMC Cancer should provide relief to women who are worried after a relative’s breast cancer diagnosis. The study shows that a family history of breast cancer does not give a useful indication of the likelihood that a woman will develop it herself at an early age.

An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies. As physicians and the general population have become more aware of this increased risk, the demand for referring healthy women with a family history of breast cancer for intensive screening or genetic testing has risen.

Geertruida H. de Bock led a team from Leiden University Medical Centre in the Netherlands who investigated whether the increased risk was significant enough to accurately predict breast cancer.

According to de Bock: “Due to the low prevalence of early breast cancer in the population, the predictive value of a family history of breast cancer was 13% before the age of 70, 11% before the age of 50, and 1% before the age of 30. These numbers are much lower than most women would probably expect.”

As the authors explain: “Applying family historyrelated criteria results in the screening of many women who will not develop breast cancer at an early age.”

Given the psychological harm that screening visits can cause, more stringent criteria should be applied to early screening. The researchers recommend that these results be used to “reassure a large number of women regarding their personal breast cancer risk”.

● A family history of breast cancer will not predict female early onset breast cancer in a population-based setting: G. H. De Bock et al. BMC Cancer – www.biomedcentral.com/bmccancer



Culture sensitive info helps type 2 diabetics

Using community-based health services, giving culturally appropriate information within samegender groups and adapting dietary and lifestyle advice to fit a particular culture can help people with type 2 diabetes control their blood sugar levels, certainly for up to six months, following health education. This conclusion was reached by a team of Cochrane researchers after they considered the data in 11 trials that involved 1,603 people.

Type 2 diabetes is a particular problem for minority ethnic groups who originate from developing countries, but live in upper-middle income or high income countries. These people tend to have low socioeconomic status and find that they are faced with many physical, communication and cultural barriers that make it difficult to access healthcare effectively.

The researchers found 11 trials where people had deliberately tried to overcome cultural barriers. In short-term studies, culturally appropriate health education programmes led to improved blood-sugar control within 3 months. This benefit was still seen when the 6-month trial periods ended. Knowledge about diabetes and healthy lifestyles also improved over this time period. Oneyear later, however, the benefits had not been sustained.

“These are important and encouraging results. They show that providing culturally tailored information can help people control their diabetes.” says Kamila Hawthorne, who works at the Department of Primary Care and Public Health at the University of Cardiff, UK.



Laser better than corticosteroids for macular edema

A promising new drug therapy used to treat abnormal swelling in the eye – a condition called diabetic macular edema – proved less effective than traditional laser treatments in a study funded by the US National Eye Institute (NEI).

The study, published online in July in the journal Ophthalmology, demonstrates that laser therapy is not only more effective than corticosteroids in the long-term treatment of diabetic macular edema, but also has far fewer side effects. Diabetic macular edema occurs when the centre part of the eye’s retina, called the macula, swells – possibly leading to blindness.

Ophthalmologists traditionally use lasers to reduce the swelling in areas of the macula. However, starting around five years ago, early reports of success in treating diabetic macular edema with injections of a corticosteroid called triamcinolone led to the rise in popularity of this alternative therapy. This is the first study to compare the long-term benefits of both treatments and evaluate their potential side effects.

While triamcinolone was used in this study, there is no scientific rationale at this time that one corticosteroid preparation should be substantially different from another.

“Results of this study should confirm the use of laser treatment for diabetic macular edema and will have a significant impact on quality of life for tens of thousands of people being treated for diabetic macular edema each year," said to Paul A. Sieving, MD, PhD, director of the NEI.

Only diabetic macular edema was examined as part of this study. Macular edema from conditions other than diabetes may respond to corticosteroid treatment and laser treatment differently.

“Many of the investigators were surprised by the results,” said Dr Michael Ip, associate professor of ophthalmology at the University of Wisconsin, and chair of this protocol for the Diabetic Retinopathy Clinical Research Network (DRCR.net). “These findings substantiate the importance of laser treatment in the management of diabetic macular edema.”

● For more information on the Diabetic Retinopathy Clinical Research Network visit: www.drcr.net



Researchers discover how herpes remains dormant

Researchers at Duke University Medical Center in the United States have discovered how the cold sore virus – the herpes simplex virus 1 (HSV1) which causes the painful sore on the mouth – hides during its inactive phase. The finding may enable scientists to figure out how to kill it.

The virus lies dormant in the trigeminal nerve of the face until triggered to reawaken by excessive sunlight, fever, or other stresses.

“We have provided a molecular understanding of how HSV1 hides and then switches back and forth between the latent and active phases,” said Bryan Cullen, Duke professor of molecular genetics and microbiology, corresponding author of the study.

His group’s findings, published in Nature (2 July 2008), also provide a framework for studying other latent viruses, such as the chicken pox virus, which can return later in life as a case of shingles, and herpes simplex 2 virus, a genitally transmitted virus that also causes painful sores, Cullen said.

● MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs, B Cullen et al – Nature, 2 July 2008, doi: 10.1038/nature07103



Give antibiotics within hour before surgery in children

Giving children preventive antibiotics within one hour before they undergo spinal surgery greatly reduces the risk for serious infections after the surgery, suggests a Johns Hopkins study published in the August issue of Pediatric Infectious Disease Journal.

Children who received antibiotics outside of the golden one-hour window were three and half times more likely to develop serious infections at the surgery site, researchers report, pointing out that something as simple as ensuring that a child gets timely prophylaxis can prevent serious complications and reduce the length of hospital stay.

“When it comes to preventing infections, when a child gets antibiotics appears to be one of the most critical yet most easily modifiable risk factors, and may matter just as much as the type and dosage of the medication,” says lead researcher Aaron Milstone, MD, infectious disease specialist at the Johns Hopkins Children’s Center, US.

Nearly 780,000 postsurgical infections occur in the United States each year, according to estimates from the Institute for Healthcare Improvement.

An infection after surgery nearly doubles a patient’s risk of death and doubles a patient’s hospital stay, researchers say. While preoperative antibiotic prophylaxis is standard in adults, there are no standard guidelines on how to administer antibiotics in children undergoing surgery.

Reviewing nearly 1,000 spinal fusion surgeries performed in children over a six-year period at Hopkins, investigators found 36 deep surgical site infections. More serious than superficial skin infections, these can cause serious complications and require aggressive treatment including additional surgeries and long-term antibiotics.

Of the 36 cases, 28% received medication outside the onehour window, either more than an hour before incision or after the surgery began. Other factors affecting infection risk included underlying medical conditions and previous spinal surgeries, researchers found.

Even though spinal fusion surgeries are complex procedures and thus carry higher risk for deep-site infections, the findings are likely relevant to many types of surgical procedures, the researchers say, because timing is always critical when administering antibiotics, either as treatment or prevention.

● Timing of Preoperative Antibiotic Prophylaxis: A Modifiable Risk Factor for Deep Surgical Site Infections After Pediatric Spinal Fusion, Aaron M. Milstone et al, – Pediatric Infectious Disease Journal, August 2008



Leishmaniasis parasites exploit immune response

Cutaneous leishmaniasis, a disease characterised by painful skin ulcers, occurs when the parasite Leishmania major, or a related species, is transmitted to a mammalian host by the bite of an infected sand fly.

In a new study from the US National Institute of Allergy and Infectious Diseases (NIAID), scientists have discovered L. major does its damage by not only evading but also by exploiting the body’s woundhealing response to sand fly bites, as reported in the 15 August 15 issue of Science.

“This work changes the textbook picture of the lifecycle of the leishmaniasis parasite, identifying the inflammatory cell known as the neutrophil as the predominant cell involved during the initiation of infection,” says NIAID Director Anthony S. Fauci, MD.

Employing advanced microscopy techniques, which allowed real-time imaging of the skin of living mice infected with L. major, NIAID researchers collaborators Nathan C. Peters, PhD, and Jackson Egen, PhD, found that the neutrophils – white blood cells that ingest and destroy bacteria – play a surprising role in the development of the disease.

Neutrophils were rapidly recruited out of the circulating blood and into the skin of infected mice, where they swarmed around the sand fly bite sites and efficiently engulfed the parasites. But unlike many other infectious organisms that die inside neutrophils, L. major parasites appear to have evolved in a way to evade death, actually surviving for long periods of time inside the neutrophils.

Eventually the parasites escape from neutrophils and enter macrophages, another immune cell population in the skin, where they can establish longterm infection. “Parasites transmitted by sand flies to mice lacking neutrophils have more difficulty establishing an infection and surviving.

This demonstrates the importance of neutrophils at the site of an infected sand fly bite and suggests the unexpected path taken by the parasite from sand fly to neutrophil to macrophage is a critical component of this disease,” says researcher Nathan C. Peters, PhD.

In addition, says researcher Jackson Egen, PhD, the study reveals how neutrophils leave locally inflamed blood vessels and move into tissues; provides new information on the movement of these immune cells within damaged tissue environments and upon contact with pathogens; and provides video images revealing active neutrophil entry into areas of damaged skin.



Researchers view sarcomeres in action

Using an unusual microscope with a tip the size of a needle, Stanford University researchers are now able to look at tiny fibres of working muscles in live humans, with minimum discomfort to the patient.

This microendoscopy technique for viewing sarcomeres – microscopic lengths of muscle fibre about 3 millionths of a metre long – has advantages over the uncomfortable alternative, a muscle biopsy in which a portion of the muscle is removed for examination.

Sarcomeres are the basic contracting engines of muscle. They generally pull in a coordinated fashion, but out-of-sync sarcomeres are implicated in muscular dystrophy and other diseases of diminished muscular control. It is thought that disease may change the length of sarcomeres and cause havoc with muscle control because the force exerted by muscle is critically dependent on length.

To observe sarcomeres in action, researchers from Stanford’s Bio-X program have devised a needle-thin probe, which is inserted through the skin into muscle. When a flash of finely tuned laser light is sent through the probe, the sarcomeres respond with light of their own to form a snapshot of muscle in action. The researchers see the images in real time on a display screen. A change in the depth of focus of the rapidly scanning device can provide a threedimensional movie.

“This is a method that does not require any operative procedures,” said Mark Schnitzer, an assistant professor of biology and of applied physics. For the first time, “it allows us to view individual sarcomeres in live humans”.

The breakthrough was reported online in the journal Nature on 6 July 2008. The technology could prove useful in understanding how muscles are altered by spinal cord injuries or strokes as well as muscular diseases, according to another of the researchers, Scott Delp, a professor of bioengineering and of mechanical engineering and, by courtesy, of orthopaedic surgery. Other areas of interest include biomechanics, orthopaedic reconstructions, prosthetic devices and tendon transfers, in which tension adjustments are a crucial element for patients relearning how to walk or grasp.



Cord traction better in Caesarean deliveries

In Caesarean deliveries the placenta is usually removed by hand or by a technique known as ‘cord traction’. A recent systematic review by Cochrane researchers shows that cord traction poses less risk to the mother than manual removal.

Removal of the placenta in Caesarean births may affect a woman’s chance of complications such as endometritis (infection of lining of the womb) and post-operative bleeding. One possible cause of endometritis is that bacteria on the surgeon’s gloves are carried into the womb during manual removal of the placenta.

In cord traction, the surgeon’s hand doesn’t enter the womb. Instead the woman is given oxytocin and external massage, which detach the placenta and it is then pulled from the womb by gentle traction on the umbilical cord.

The new study compares the advantages of the two techniques. Researchers reviewed 15 trials involving a total of 4,694 women and found that there was an increased risk of endometritis and high blood loss in Caesareans where the placenta was removed by hand. Women who had manual removal also stayed in hospital longer after their operations.

“Although cord traction may take a little bit longer, there are clear health benefits of this method over manual removal of the placenta,” says lead researcher Rose Anorlu, a gynaecologist at the College of Medicine of the University of Lagos in Nigeria.



Trial casts doubt on Vytorin efficacy

In a notice issued late August, the US FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer.

Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis.

A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.

The FDA recommends healthcare professionals and caregivers should continue to monitor patients taking Vytorin. The Agency said it expects to give a final evaluation in about 6 months.

● For more info check: www.fda.gov/medwatch



Ethics of clinical trials in developing world questioned

Early stage gene therapy clinical trials are recruiting patients from the developing world, providing medically deprived populations access to interventions that show promise but have largely unknown effects in humans.

According to commentary by bioethicists at Carnegie Mellon and McGill universities published in the 7 July 2008 issue of The Lancet, the practice may be inconsistent with international ethics guidelines on justice. “There are many reasons why researchers might look to the developing world for research subjects,” said Alex John London, lead author of Justice in Translation: from Bench to Bedside in the Developing World and director of Carnegie Mellon’s Center for the Advancement of Applied Ethics and Political Philosophy.

“But serious ethical issues can arise when research relies on the deprivations experienced by people living in developing countries to advance research that is not responsive to the urgent health needs of their communities.” London and his co-author, Jonathan Kimmelman, an assistant professor in McGill’s Biomedical Ethics Unit, urge organisations that sponsor research in low- and middleincome countries (LMICs) to ensure that they are addressing the most pressing health needs of those nations.

The article also notes that any interventions developed as a result of such research should be affordable and easily implemented in those countries’ healthcare systems. While other authors have explored ethical issues in later stage clinical trials, in which the interventions have already been deemed safe and effective, for the most part, London and Kimmelman are the first to discuss the more complicated considerations surrounding the riskier earlystage research.

“Our report centres on complex agents like gene therapies that are being tested for the very first time in human beings,” Kimmelman said. Researchers have various reasons for turning to developing nations for clinical trial subjects. In some cases, patients are recruited because diseases like malaria were much more common in LMICs. In other cases, diseases are so rare as to necessitate worldwide recruitment.

However, some trials also appear to have recruited patients who did not have access to treatments routinely available in developed countries. Such patients provide a pool of “treatment naïve” subjects that would not otherwise be available to researchers. Treatment-naïve subjects are particularly valuable, as they offer the opportunity for researchers to observe an intervention’s behaviour on a blank canvas, of sorts.

“Our goal is not to curtail research in low and middleincome countries,” said London, who is also an associate professor of philosophy at Carnegie Mellon. “It is to make sure that project sponsors give careful consideration to the relationship between a particular research study and the needs of the communities from which study participants are drawn.”