Symposium on Publishing Clinical Trials
What: A one-day symposium jointly organized by the Institute of Clinical Research and the European Medical Writers`Association.
Theme: Publishing Clinical Trials: Ethics and the Pharmaceutical Industry.
When and where: 27 February 2008, Novotel Hammersmith, 1 Hammersmith International Centre, London.
“This symposium will be presented by a panel of experts including medical writers, journal editors, academics and pharmaceutical industry managers. Topics will include publication policy, ghostwriting, fraud and other ethical issues of publishing clinical trials.”
Details and registration at www. icr-global.org
Clinical predictors of severe illness in neonates
In a multinational study, researchers evaluated 3177 aged 0-6 days old and 5712 infants aged 7 to 59 days old admitted to healthcare centers in Bangladesh, Bolivia, Ghana, India, Pakistan, and South Africa. They recorded the clinical signs and symptoms and evaluated the “sensitivity, specificity, and odds ratio (OR) for each symptom and sign individually and combined into algorithms to assess their value for predicting severe illness.” Jaundice was excluded in the analysis.
Results showed 12 independent clinical predictors of severe illness that would indicate the need for hospitalization in the 0–6 days age-group. These clinical signs are as follows:
1. History of difficult feeding
2. History of convulsions
3. Movement only when stimulated
4. Fast respiratory rate (≥60)
5. Severe chest indrawing
6. Pyrexia (>37.5 °C)
7. Low body temperature (<35.5)
8. Lethargy
9. Prolonged capillary refill
10. Grunting
11. Cyanosis
12. Stiff limbs
These predictors were also shown to be sensitive in the older age group.
To simply decision-making for primary care practitioners, the number of clinical signs indicative of the need for hospitalization was reduced, taking into account only the first seven in the list. This reduction did not significantly reduce the sensitivity of the check list.
Source:
Clinical signs that predict severe illness in children under age 2 months: a multicentre study. The Young Infants Clinical Signs Study Group. The Lancet 2008; 371:135-142.
ENHANCE trial update: no beneficial effects on CA IMT from ezetimibe
The much-awaited results of the “Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression” (ENHANCE) trial are finally out – and they are a huge disappointment.
ENHANCE is an international 2-year, randomized, double-blind, controlled trial which compared the combination of ezetimibe and simvastatin to simvastatin monotherapy.
Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor routinely used in the management of atherosclerosis. The newcomer ezetimibe is a specific cholesterol absorption inhibitor and the 2 drugs supposedly act as complementary agents that can have beneficial effects on the carotid artery intima-media thickness (CA IMT) of atherosclerosis patients. The trial was conducted in 720 patients with heterozygous familial hypercholesterolemia. The primary end point was mean change in the IMT measured at 3 different sites in the carotid arteries [1].
The trial results showed no significant difference in the mean IMT change between patients treated with ezetimibe/simvastatin 10/80 mg vs patients treated with simvastatin 80 mg alone. There was also no significant difference in treatment-related adverse events in both treatment groups. However, ezetimibe was associated with a larger reduction in LDL cholesterol [2].
References:
1. Kastelein et al., 2005. Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial. American Heart Journal 149 (2): 234-239.
2. Hughes, S. 2008. ENHANCE results yield disappointment for ezetimibe. Heartwire 14 Jan 2008.
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Bisphenol A contamination in plastic bottles
Plastic water bottles were taken off the shelves in Canada last month and caused concerns worldwide. The offending substance in the bottles is bisphenol A (BPA), an endocrine-disrupting chemical (EDC). In the latest issue of Toxicology Letters, American researchers published the results of their research on the health risks of BPA [1].
BPA is “an estrogenic high-production chemical used primarily as a monomer for the production of polycarbonate and epoxy resins.” Bioactive BPA is released from polycarbonate bottles at rates ranging from 0.20ng/h to 0.79ng/h. There is no significant difference in the BPA migration rates in new and used bottles at room temperatures. At 100°C (e.g. contact with boiling water), the migration rates increased by up to 55-fold. The estrogenic bioactivity of the BPA-like immunoreactivity released into the water samples was confirmed using an in vitro assay of rapid estrogen signaling and neurotoxicity in developing cerebellar neurons.
Based on these findings, the following conclusions can made:
- Food and beverages which come in contact with epoxy resins or polycarbonate plastic containers may be contaminated by bioactive BPA.
- Human exposure to BPA is actually widespread and the substance should therefore be as a contributing source to the total “EDC-burden”.
This is not the first study to investigate the migration of PBA. However, there are differing opinions whether the amounts released are high enough to present a health risk. Aside from plastic bottles, other BPA sources are polycarbonate dental products and food packaging [2].
Sources:
1 Le HH, Carlson EM, Chua JP, Belcher SM., 2008. Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicol Lett. 2008 Jan 30;176(2):149-56. Epub 2007 Nov 19.
2 Howdeshell KL, Peterman PH, Judy BM, Taylor JA, Orazio CE, Ruhlen RL, Vom Saal FS, Welshons WV., 2003. Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environ Health Perspect. 2003 Jul;111(9):1180-7.
The First Rapid Blood Test for MRSA is in the Market
In recent years, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection have been on the rise. This has especially become a problem in hospitals where MRSA infections have become synonymous to healthcare-associated infections.
S. aureus is a very common bacterial species that causes pimples and mild skin and wound infections. However, years of antibiotic use gave rise to strains which are resistant to the antibiotic methicillin as well as to other drugs. The MRSA strains can cause life-threatening conditions such as sepsis, infections of surgical sites, and pneumonia.
The US FDA has recently approved the first quick test to identify MRSA in the blood. Using molecular methods, the BD GeneOhm StaphSR Assay can detect genetic material from the common, less dangerous methicillin-sensitive S. aureus (MSSA) as well as the drug-resistant deadly MRSA strains [1, 2]
Early detection of MRSA infections is crucial in their treatment and management. Using standard diagnostic laboratory tests, it takes 2 days to identify MRSA in blood samples. With the new rapid test, results are available within 2 hours. This is especially good news to the public health community which had to deal with the rapid rise in the incidence of MRSA infections in hospitals and clinics. Immunocompromised patients are especially susceptible.
The BD GeneOhm StaphSR test is manufactured by BD Diagnostics, a subsidiary of BD of Franklin Lakes, N.J.
[1] FDA News, 2 Jan 2008. FDA Clears First Quick Test For Drug-Resistant Staph Infections.
Passive smoking and allergies in children
Study design and objective
The aim of this prospective birth cohort study was to investigate the relationship between in utero and postnatal exposure of children to environmental tobacco smoke and IgE-sensitization.
Study population and primary end-points
The study was conducted in Stockholm, Sweden and followed-up families with young children. A total of 4089 families participated and answered questionnaires which survey smoking habits in the family and allergic symptoms in the children. Questionnaires were completed when the children was aged 2 months, 1, 2 and 4 years old. Blood tests for IgE antibodies to common food and inhalant allergens were performed at age 4 years.
Results
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Early exposure of children to environmental tobacco smoke was significantly associated with increased risk for sensitization to mold, cat, horse, and food allergens at 4 years but not to seasonal allergens such as pollens.
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A dose-response relationship for passive smoking exposure at 2 months and IgE sensitization was observed.
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IgE sensitization was strongest in cases of biparental smoking, followed by maternal smoking, and then paternal smoking.
Weakness of the study
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There is a difficulty in distinguishing the effects of prenatal from postnatal exposure to tobacco smoke.
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There might be bias due to the common and early use of daycare facilities in
Sweden. 75% of the study cohort was at daycare centers by age 2.
The study was funded by the Swedish Heart and Lung Foundation, Stockholm County Council, the Gillbergska Foundation and the Swedish Asthma and Allergy Foundation, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Research Council.
Source:
The newest beta-blocker: will it sell?
It is the 19th of its kind in the market. No wonder cardiovascular experts were not that excited when the US FDA approved the selective beta-blocker Bystolic (nebivolol) this month [1].
However, nebivolol has some characteristics that other beta-blockers don’t have.
Efficacy
Nebivolol offers a new treatment option for hypertension through its “added pharmacological properties of producing vasodilation and reducing total peripheral resistance brought about by modulation of nitric-oxide release.” These properties make the drug more effective than traditional beta-blockers [2].
Safety
Compared to traditional beta-blockers, nebivolol causes relatively lower incidence of side effects normally associated with this class of drugs [1,2]. “Nebivolol is a so-called vasodilating beta blocker. Thus, in contrast to traditional beta blockers, it is more patient friendly in that it maintains systemic flow and blood flow to target organs, lowers vascular resistance, and has very little, if any, metabolic adverse effects”, according to one expert [2].
Both the manufacturer (Mylan Bertek Pharmaceuticals) and the marketing company (Forest Laboratories) hope these properties would be the selling point to make the drug attractive to both doctors and patients.
The main competitors of nebivolol would be the similar but non-selective beta-blocker carvedilol as well as cheap generics.
Sources:
Cluster of human avian flu cases in Pakistan
The recent H5N1 outbreak in Pakistan causes much concern because it is the largest cluster of human cases of the avian flu since 2006 in Indonesia. 8 suspected cases have so far been reported in the outbreak, 2 of which were fatal.
The World Health Organization, in cooperation with Pakistani health officials, is closely monitoring the area, as well as checking hospital and clinic registers for possible unreported retrospective cases. Cases clustered closely in a small geographical area are highly crucial in the epidemiological monitoring of avian flu because they may represent cases of the human-to-human transmission of the disease. To date, transmission has only been reported from animal-to-animal and from animal-to-human.
Nature News, 17 Dec 07
WHO news, 15 Dec 07
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Recalls and OTC Disapproval: A Gloomy December for Merck
This is definitely not Merck’s month.
On 12 December 2007, Merck announced the voluntary recall of potentially contaminated batches of the influenza vaccines PEDVAXHIB and COMVAX. These vaccines are indicated for infants and young children for protection against the seasonal flu and hepatitis B. The affected batches were distributed in April 2007 [1].
On another front, a US FDA advisory panel voted against Merck’s application for the prescription drug Mevacor 20 mg to be sold over-the-counter. Mevacor (lovastatin) is indicated for the treatment of elevated cholesterol levels. It has been on the market as a prescription drug since 1997. The panel’s recommendation is based on concerns of the use of the drug by misinformed consumers who may not actually benefit from it. The recommendation is not binding and a final decision would be reached in January 2008 [2].
Merck News Item, 12 Dec 2007
Merck News Item, 13 Dec 2007
Symposium on antiviral applications of RNAi
The European Science Foundation (ESF) and the European Molecular Biology Organization (EMBO) are organizing a symposium on “Antiviral Applications of RNA Interference” on 5 to 10 April 2008.
The symposium will take place in Sant Feliu de Guixols, Spain, located 120 km north of Barcelona.
RNA interference (RNAi) is a promising new technology with a great potential for use as an antiviral tool. The approach allows specific inhibition of gene expression either through the degradation of specific RNA molecules or hindering of transcription of certain genes. The first clinical trials to evaluate the efficacy and safety RNAi technologies have recently been started.
The symposium will mainly focus on human pathogenic viruses and “will be the first comprehensive meeting combining RNAi and antiviral research.”
“The meeting will cover the most recent progress in the field by 22 invited presentations of internationally renowned researchers, complemented by shorter contributed oral presentations of young scientists and by poster presentations.”