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.”
Nonclinical Studies: The Latest in Adult Stem Cell Research in Mice
In the latest issues of Nature and Science, two articles report on promising therapies using adult stem cells.
American and German researchers demonstrated that embryonic stem cells can mend post-infarction heart muscles without causing ventricular tachyarrhythmias. Following cardiomyocyte implantation, mice were protected against the induction of ventricular tachycardia. This was not evident when adult and bone marrow stem cells were used in the engraftment. The reason may be the fact that embryonic heart stem cells have a high degree of expression of the gap-junction protein connexin 43. Bone marrow stem cells engineered to express this protein afforded similar protection [1].
In another in vivo study, researchers successfully treated sickle-cell anemic mice using adult murine stem cell lines. The test mice were genetically-engineered to have a sickle-cell hemoglobin allelle, producing a “humanized sickle cell anemia mouse model.” The adult stem cells from these animals were reprogrammed to become pluripotent and their faulty allele was corrected by gene-specific targeting. Following transplantation of these reprogrammed and corrected cells, treated mice exhibited higher RBC counts and hemoglobin levels than control mice [2].
The results of these studies demonstrate potential cell-based therapies using adult stem cells.
[1] Roell, W. et al. Nature 450, 819-824 (6 December 2007)
[2] Hanna, J. et al. Science doi:10.1126/science.1152092 (6 December 2007)
The STEP Trial: Discontinuation and Unblinding
The STEP Trial: The STEP study was a phase II multinational, randomized, double-blind, placebo-controlled clinical trial which was started in 2004.
The Investigational Drug: The V520 HIV vaccine candidate is a combination of 3 components made from a weakened adenovirus type 5. The vaccine serves as a vector of 3 synthetically produced HIV genes known as gag, pol and nef. These HIV genes would supposedly induce “an HIV-specific immune response through the body’s own CD8 T-cells, which become programmed to recognize and kill HIV infected cells.”
The Sponsors: The STEP trial was sponsored by Merck, the National Institute of Allergy and Infectious Diseases (NIAID), and the HIV Vaccine Trials Network (HVTN).
The The Study Population: 3,000 HIV-negative participants from different ethnic groups. They are aged between 18 and 45 years of age and at high risk of HIV infection. The trial was conducted in the United States, Peru, Brazil, Dominican Republic, Haiti, Jamaica, Australia, and South Africa.
The Efficacy Endpoints: The primary efficacy endpoints were to evaluate the ability of the vaccine to prevent HIV infection and to reduce virus proliferation in infected individuals.
The Discontinuation: On 21 September 2007, Merck announced the discontinuation of the STEP study due to poor efficacy profile. The vaccine did not prevent infection nor reduce viral loads in the bloodstream of HIV-positive individuals.
The Unblinding: In November 2007, Merck and HVTN announced their decision to unblind the trial based on concerns that the vaccine may actually have induced susceptibility to HIV infection in study participants. Sources:
HVTN Press Release 13 Nov 2007
Nexavar Approved for Liver Cancer Treatment
The US FDA has recently approved the oral kinase inhibitor Nexavar (sorafenib) for use in patients with hepatocellular carcinoma, an inoperable form of liver cancer. This makes Nexavar the “first FDA-approved drug therapy for liver cancer.” Nexavar was originally approved in 2005 for treatment of advanced kidney cancer and is currently marketed in over 60 countries for this indication [1, 2].
The FDA approval came about month after Nexavar was centrally approved in Europe in October for the new indication. The appproval was based on results of a randomized placebo-controlled trial involving 602 patients with hepatocellular carcinoma. The study results showed an average extended survival of 2.8 months in patients treated with Nevaxar compared to placebo. Tumor progression was also observed to be slower.
“Nexavar, an oral anti-cancer drug, is the first approved systemic drug therapy for liver cancer and the only drug therapy shown to significantly improve overall survival in patients with the disease.” [1,2]
Nexavar is manufactured by Bayer Pharmaceuticals Corporation of Germany.
[2] Bayer Press Release, 19 Nov 2007
Sanofi-Aventis Joins Forces with Regeneron
The French pharmaceutical giant Sanofi-aventis is joining the biotech bandwagon. Initially thought to be a slowmover in the biotech field, it is now stepping up its drug development program and is particularly concentrating on the development of therapeutic antibodies.
In order to attain these goals, Sanofi-aventis has decided to increase its stake in the biotech company Regeneron from 4% to 19%. As part of the payment, Sanofi-aventis will fund a big part of research costs in the next five years. Research will focus on the development of fully human monoclonal antibodies [1, 2].
Part of the colloboration portfolio are two promising drugs, namely:
- Antibody to Interleukin-6 receptor (IL-6R), indicated for rheumatoid arthritis, currently undergoing Phase I clinical trials.
- Antibody to Delta-like ligand-4 (Dll4), indicated for tumors, to enter clinical development in 2008.
From this collaboration, Sanofi-aventis aims to develop about 20 drug candidates annually and targets about 30 new drug submissions by the end of 2010 [1,2].
[1] 29 Nov 2007, Sanofi-aventis press release
[2] 29 Nov 2007, Regeneron press release