Asthma is common in first world nations, unheard of in the developing world and rising quickly in countries making the transition.

Many theories have been posited to explain this association. They range from the idea that clean living somehow revs-up the immune system to a belief that swimming pool chemicals bring on the allergy-mediated condition.

The common denominator is that environmentally mediated phenomena associated with economic development are directly triggering asthma.

Shadmehr Demehri and colleagues at Washington University in St. Louis have postulated an indirect link, in which environmental factors trigger eczema, a benign though annoying skin condition, and the distressed skin cells create chemical signals that in turn trigger asthma. 

Eczema is also linked to economic development. Nearly 17% of US children have it, and nearly 70% of children with eczema develop asthma, even though the prevalence of the letter condition in the general population is only 4-8%.

Demehri’s team believes the culprit is thymic stromal lymphopoietin (TSLP), an immune-stimulating molecule released by skin cells when they are damaged, as by eczema. TSLP, they theorize, causes lung tissue to over-react to allergens, which leads to asthma.

The team wrote-up the results of 3 experiments in the Public Library of Science Biology that provide support for its hypothesis.

First, the scientists showed that mice genetically engineered to develop eczema were prone to develop asthma. Then they deleted the gene coding for the TSLP receptor in the bronchial tissue of such mice and voila, the new editions did not develop asthma.

In the third step, the scientists created mice that over-produced TSLP in the absence of skin problems. These mice wheezed up the wazoo.

Case closed, at least in mice. Eczema is easily treated, by the way, with low-dose topical steroids.

New Jersey-based drug giant Merck & Co. announced last week it will not seek FDA approval this year for a heart-failure drug after preliminary results from a late-stage study showed the stuff didn’t meet efficacy targets.

In 2007, Merck acquired the drug, rolofylline as part of its $366 million buy-out of NovaCardia. 

It was the latest in a series of hits to the company’s  late-stage drug pipeline which was described by Sanford Bernstein analyst Timothy Anderson as “uninspiring” in a memo to investors after the announcement.

Three months ago, Merck said it was postponing near-term plans to seek approval for its migraine fix, telcagepant, after safety concerns surfaced in a mid-stage study. In 2008, the FDA asked Merck to wait until a large trial concluded in 2013 before seeking approval for Cordaptive, a cholesterol-buster.

In addition, Merck recently shelved its early-stage obesity drug, taranabant due to a lousy side effect profile.

Merck spokesperson Ronald Rogers scoffed at criticisms of his company’s pipeline.

In fact it has a “strong track record of bringing new products to market,” he told the Wall Street Journal, citing the diabetes drug Januvia, the HIV-fighter Isentress, and Gardasil and Zostavax, the vaccines for cervical cancer and shingles, respectively.

The recent setbacks have highlighted the importance of Merck’s plan to acquire the Plough for $41 billion, a deal that should close in Q4. Both companies are fired up about 2 potential blockbuster drugs in the Plough’s pipeline—the clot-buster TRA and the arthritis drug golimumab (aka Son of Remicade).

Merck’s asthma drug, Singulair, accounts for 18% of the company’s revenues. It loses patent protection 3 years from now.

In 1924, Johns Hopkins biologist Raymond Pearl published a U-shaped graph showing high death rates for heavy drinkers and abstainers, and lower death rates among moderate drinkers.

Since then, hundreds of observational studies have confirmed the association and suggested reasons for it.

The juice is purported to reduce coronary disease, for example, because it increases HDL cholesterol and has anti-clotting effects.

Moderate alcohol consumption is also associated with slower cognitive decline in the mildly impaired elderly and improved bone mineral density in elderly women. In addition, light drinkers tend not to develop diabetes, and that those with diabetes tend not to develop coronary disease.

Could all this research be wrong?

“The moderate drinkers tend to do everything right — they exercise, they don’t smoke, they eat right and they drink moderately,” affirmed Kaye Fillmore, a retired sociologist from UCSF. “It’s hard to disentangle all of that, and that’s a problem.”

And alcohol consumption, even at moderate levels, has a dark side. It has been linked to multiple cancers, fatal accidents, neuropathies and of course, liver disease.

That’s why health guidelines on the matter walk a fine line. The American Heart Association warns that people should not start drinking to protect themselves from cardiac disease. And the US dietary guidelines hedge goes something like this: “alcohol may have beneficial effects when consumed in moderation.”

A confounding factor is that at least some studies showing a beneficial association were funded by the alcohol industry.

A few years ago for example, BU physician Curtis Ellison hosted a conference on the subject and published a summary one year later. The summary indicated the attendees had reached a “consensus” that moderate drinking “has predominantly beneficial effects on health.”

The meeting, as well as much of Ellison’s work, was partially financed by the industry, according to the New York Times. And the summary itself was co-authored by Marjana Martinic, a senior VP for the International Center for Alcohol Policies, an industry-supported group. Yeesh!

The Food and Drug Administration is mad as hell about illegal products marketed over the Internet claiming to diagnose, prevent, mitigate, treat or cure the 2009 H1N1 (Swine) flu virus.

And it’s not going to take it anymore.

The FDA has warned consumers to stay away from Swine flu products that it has not approved, cleared, or authorized, and beginning in May, it warned more than 50 offending Web site operators to cut it out (see full list here).

Approximately 66% of them did so.

That wasn’t good enough for FDA Commissioner Margaret Hamburg. In a press release last week she said “we are committed to pursuing those who attempt to take advantage of a public health emergency by promoting and marketing unapproved, or unauthorized products. We will (continue) our efforts to protect consumers from these fraudulent, potentially dangerous products.”

The bogus products targeted by the FDA include:
- A shampoo claiming to protect against H1N1,
- A dietary supplement claiming to protect infants and children from H1N1,
- A supplement claiming to cure H1N1 in 4-8 hours,
- A spray claiming to leave a layer of ionic silver on one’s hands that killes the virus
- Several tests claiming to detect the virus, and
- An electronic instrument costing thousands of dollars claiming to use “photobiotic energy” and “deeply penetrating mega-frequency life-force energy waves” to strengthen the immune system and prevent symptoms associated with H1N1.

The scammers were discovered during Internet sweeps undertaken by the several FDA departments and other agencies.

The FDA has threatened to take civil or criminal enforcement action against vendors that fail to comply with the marching orders.

Kids who take Ritalin and Adderall for ADHD are much more likely than their drug-free counterparts to die suddenly, according to scientists at Columbia University.

Still, the number of deaths in the drug-taking population was small, and limitations in the study prevented the scientists from concluding the popular medicines were causing kids to drop dead.

Physicians have long wondered whether such a link could exist because the drugs are stimulants: they increase heart rate and blood pressure and occasionally precipitate abnormal heart rhythms.

About 2.5 million children take these drugs in the US.

“This study reports a significant association between sudden unexplained death and the use of stimulant medication, specifically methylphenidate (Ritalin),” wrote the authors. Our findings draw attention to the potential risks of stimulant medications for children and adolescents.”

To reach these conclusions, Madelyn Gould and colleagues undertook a matched case-control study involving 564 US children that died suddenly and inexplicably between 1985 and 1996.

The scientists determined which children were taking the stimulants through interviews with parents and a review of medical records.

While kids taking the stimulant medications had a much higher risk of sudden death, the tragic event occurred in less than 1 in 10,000 kids taking the drugs. And it remained possible that ADHD itself might have increased the risk for sudden death.

For those reasons, FDA officials said it would not be necessary to change the warning labels on the drugs and urged parents to take up any concerns with doctors rather than stopping their kids’ drugs cold turkey.

The new safety concerns regarding ADHD drugs come on the heels of an unsightly public dust-up involving co-authors on a scientific paper that appeared to show the drugs had no beneficial effects in the long term.

This post first appeared on the Practice Fusion Blog.

Last week, the venerable Institute of Medicine released a list of 100 research priorities designed to provide a roadmap for the comparative effectiveness agenda mandated by the Big O’s January Hail Mary otherwise known as ARRA.

At the top of the list are treatment strategies for common conditions like obesity and back pain and the prevention of falls in hospitalized patients. The list also includes mechanisms by which  medical research findings are disseminated to the bedside and to the public.

The full list is here.

Congress allocated $1.1 billion of its $787 billion stimulus package to comparative effectiveness research, assuming such research can improve the quality of health care, though such an impact would be years away.

This “is a program about improving decisions for patients,” Harold Sox told the Wall Street Journal. Sox co-chaired the IOM committee that established the list.

Sox’ team distilled the final 100 from more than 2,600 suggestions submitted by professional groups, policy experts and the public.

Although the products of medical device and pharmaceutical companies will be the primary focus of the research, the former contributed only 11 suggestions and the latter managed just 17. “For whatever reason, we didn’t get many suggestions from them,” Sox understated.

“Right now, the winners and losers (among the various drugs and devices in extant) are based on which company has the best marketing department, rather than who has the best product,” said University of Pennsylvania professor Brian Strom.

“If we show that in certain drugs, the more expensive one is better than the cheaper one, the answer is use the expensive one,” added Strom. “The focus of comparative effectiveness research is that it leads to better care, not cheaper care.”

A study of children between the ages of 11 and 17 has revealed that suicide risk increases with the number of changes in residence.

To reach this conclusion, Ping Qin and colleagues from the University of Aarhus used data from Danish population registries to identify 120,000 children born in Denmark between 1978 and 1995.

Using other sources, they subsequently determined  that 4,160 of these people attempted suicide during adolescence. Seventy-nine completed the act.

The scientists then used logistic regression to demonstrate the increased risk of attempted and completed suicide associated with changes in home address. The more frequently the kids moved, the higher was the suicide risk.

Subjects that moved more than 3 times had twice the risk of suicidal behavior as those that stayed put throughout their early years. Those who moved more than 10 times experienced a four-fold bump in such risk.

The finding was not affected by year of birth, birth order, birthplace, age when the move took place, gender, presence of 2 parents, or parental age at birth.

“It’s understandable that a lot of moves increase people’s risk for suicide,” Nadine Kaslow, the chief psychologist at Emory University told ABC news. “Moving is all about losing things.”

But Kaslow cautioned that moving might be a marker for problems rather than the proximate cause of suicidal behavior. “There could be all sorts of other family stressors that are associated with moves,” she reasoned.

The write-up appears in Archives of General Psychiatry.

“It is always good to involve children in the process, motivating their participation in all decisions, plans and practical work,” wrote the authors.

Kaslow recommended having the children visit their new home and, after the move, their old one. But she added the vast majority of children do adjust. “Some kids are at increased risk, but many…do just fine,” she told ABC News.

A prospective clinical trial of the diabetes drug Avandia has failed to clear the air regarding the blockbuster’s potential to raise cardiac risk.

GlaxoSmithKline, the drug’s maker had hoped that the so-called Record trial would quell concerns that have dogged Avandia since 2007, when a report suggested it was associated with an increased risk of heart attacks compared with other diabetes drugs.

Avandia’s annual sales fell 55% to $1.29 billion since that report surfaced.

On the surface, the Glaxo-funded trial looked promising. Newcastle University’s Philip Home and colleagues reported in last week’s Lancet that people taking Avandia did not experience increased hospitalization rates or cardiovascular mortality compared with those taking other diabetes drugs.

Home’s position on the matter, as reported by the Wall Street Journal, was that Record provided “a robust assessment of [Avandia's] cardiovascular safety.”
 
But in an accompanying editorial, Ravi Retnakaran and Bernard Zinman of Mount Sinai Hospital in Toronto said “definitive conclusions” about the drugs cardiovascular risk “remain elusive” because of the study’s methodological problems.

The cardiovascular event rate observed in Record was lower than expected, they said. That meant it wasn’t possible to reach firm conclusions.

The low event rate might have been caused by the coincident use of cholesterol-lowering statins in the Avandia group, or by the unexpectedly high patient drop-out rate from the study, which may have been prompted by safety concerns about Avandia that arose during the trial.

Roughly 45% of the subjects dropped out of the study before it concluded.

Amid the controversy, David Robbins, a professor of medicine at Kansas found a common denominator everyone could agree with. Avandia certainly did not improve cardiovascular outcomes, he reasoned to the Journal. “What we really want in diabetes is…drugs that are reducing cardiovascular events.”

The FDA will update the labels on 3 commercially-available leukotriene inhibitors to reflect post-marketing research findings that the asthma-fighters can precipitate neuropsychiatric events ranging from agitation to suicidal ideation.

Leukotrienes have become popular options for treating moderate to severe asthma.

They are usually used in conjunction with bronchodilators or inhaled steroid medications.

The new warnings will appear on the labels for Merk’s Singulair, AZ’s Accolate and Zyflo, which is made by Cornerstone Therapeutics.

Singulair dominates the category from a sales standpoint. First approved in 1998, the drug is Merck’s top revenue-producer with $4.3 billion in sales last year. The drug has been approved for both children and adults with asthma and for the treatment of certain allergies. The latter 2 are approved for asthma only.

Leukotrienes are produced by the body in response to inflammatory stimuli such as inhaled allergens.

“Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications,” read the posting on the FDA website.

Neuropsychiatric events that have been linked to leukotriene inhibitors include agitation, aggression, anxiousness, depression, hallucinations, dream abnormalities, insomnia, irritability, restlessness, suicidal ideation, suicide and tremor.

Merck released a statement saying it was “confident in the efficacy and safety of Singulair,” while adding it would revise the label as directed by the FDA.

Neuropsychiatric events other than sleep disorders and insomnia “were not commonly observed” in trial data provided by the drug makers, according to the FDA.

The FDA launched an investigation last year after receiving reports of mood and behavior changes in patients taking Singulair. It asked all 3 drug makers for all available post-marketing information, and made the call after completing that review.

Cancer research trials published in peer-reviewed journals tend to include a disproportionately small number of women, according to a study published in Cancer.

To reach this conclusion, Reshma Jagsi and her colleagues at the University of Michigan reviewed 661 prospective studies involving more than a million subjects who had non-gender specific cancers like those of the colon, head and neck, lung, brain and lymphomas.

“In the vast majority of studies we analyzed, fewer women were enrolled than we would expect given the proportion of women diagnosed with the type of cancer being studied,” Jagsi told BurrillReport.

Jagsi added, “we’re seeing it in all cancer types. We know there are biological differences between the sexes, as well as social and cultural differences. Studies need to assess whether there are differences in responses to treatment between women and men.”

The practice flies in the face of the NIH’s Revitalization Act of 1993, which highlighted the need to include women in research studies in numbers sufficient to support gender-specific subgroup analyses.

Government-funded studies did include slightly higher numbers of female participants: 41% of subjects in such trials were women, whereas only 37% of the subjects in non-government-funded studies were women.

The authors suggested several reasons for the discrepancy. For example, scientists tend to avoid including “vulnerable populations,” such as women of childbearing age in their studies. “By protecting them from research, we’re excluding them,” the scientists concluded.

Other barriers are thought to include a lack of information, fear, and a belief that the studies interfere with individual responsibilities including child care.

The authors suggest that among other things, investigators should reimburse participants for transportation and child care expenses incurred during the study.

We don’t recall Michael Leavitt saying anything like this during the 4 years he served as Secretary of HHS under George W. Bush, but now he’s quite forthright in calling Medicare a fiscal disaster, and declaring that health reform proposals built around it would end up just the same.

With surely not a whit of political intent, the former Secretary told the Washington Post today that Medicare provides uncoordinated, expensive, poor quality care because “every incentive in the system is to provide more care, not better care.”

Referring to the Big O’s fading aspiration to create a public option that would compete against Big Insurance, Leavitt scoffed that such an idea would lead to “essentially a bankrupt system.”

Building on Medicare “is the equivalent of trying to solve obesity by prescribing a perpetual regimen of double calories,” Leavitt told the Post.

Then, in a remarkably transparent sleight of hand designed to distance himself from what he just said was the abject failure of a program for which he was responsible, Leavitt pointed a finger at Congress.

It’s too soft, too beholden to the special interests, he deadpanned. 

Planned cuts in Medicare payments to physicians were continually blocked by a Congress that was, he said, in the back pockets of providers. And Congress had OK’d competitive bidding on medical equipment, but backed away from that too, amid pressure from the device industry.

“[I]n a system that’s run by the government, lobbyists and various commercial interests, including doctors, hospitals, nurses, medical equipment dealers and every other part of the system, use the political process to restrict the capacity for change,” Leavitt said, his hands thoroughly washed of the matter.

Let’s hear it for GAVI Alliance partners, the World Bank, the WHO, UNICEF, 5 national governments and the Bill & Melinda Gates Foundation, who announced last week that they have kicked-off the first-ever Advance Market Commitment (AMC) program.

The purpose of the program is to accelerate access to vaccines against pneumococcal disease, which kills 1.6 million people each year, including a million children less than the age of 5.

90% of these deaths occur in developing countries.

Pneumonia, the most common form of serious pneumococcal disease, accounts for one in 4 childhood deaths around the world. The AMC pneumococcal program may prevent up to 7 million childhood deaths by 2030.

Pneumococcal vaccine has been part of regular immunization programs in developed countries since 2000, but there is no affordable vaccine for developing countries.

The vaccine costs $70 per dose in industrialized countries but thanks to the AMC, its price in developing countries will be secured for the long-term at $3.50.

Through an AMC, donors commit money to guarantee the price of vaccines once they have been developed, thus creating the potential for a viable future market.

These commitments provide vaccine makers with proper incentives to conduct R&D and build manufacturing capacity.

“The AMC is an important step towards reducing the health inequities between rich and poor, and a way to protect the lives of the world’s poorest children,” said Julian Lob-Levyt, GAVI’s CEO. “We look forward to pharmaceutical firms applying to the AMC quickly.”

For the pneumococcal AMC program, the governments of Italy, the UK, Canada, Russia, and Norway and the Bill & Melinda Gates Foundation combined to raise $1.5 billion, and GAVI threw in another $1.3 billion. The World Bank provides fiduciary support and the WHO has established technical criteria for a suitable vaccine. UNICEF will procure and distribute it.

Companies that participate in the AMC must commit to supply the vaccines at the low price even after donor funds are gone.

Plans are to introduce the new vaccine to 60 of the world’s poorest countries by 2015.

A CDC report says chicken is the most common source of food poisoning in the US, but vegetable eaters had better beware, too.
 
According to the report, the culprit behind most poultry-related illnesses is Clostridium perfringens, a bacterium that provokes  cramping and diarrhea approximately 10 to 12 hours after the fateful swallow.

Claustridia spores can survive cooking, so maintaining poultry meat at low temperatures during processing and storage ends up being the key preventive measure.

Researchers counted leafy vegetables, root vegetables, vegetables from stalks or vines, fungi and sprouts as separate categories. Had all that produce been combined, vegetable-associated outbreaks would have far exceeded those caused by poultry.

Salmonella is the pathogen responsible for most cases of food-borne illnesses associated with vegetables. It has caused national outbreaks from contaminated peanut butter, spinach and tomatoes in the last few years.

Interestingly, viruses—which can end up on food when restaurant workers fail to wash their hands before handling it—topped straight-up food borne illnesses by almost two to one.

These viruses cause most cases of “stomach flu,” a lovely 48-hour run of nausea and vomiting that has nothing to do with the actual flu virus.

“We’re glad that CDC is finally coming out with good attribution data,” Caroline Smith DeWaal told the New York Times. The director of food safety at Science in the Public Interest added, “it shows the need for improvement, not only at FDA but at the USDA’s food safety programs as well.”

The findings were based on an analysis of reports submitted to the CDC by state and local health departments. Unfortunately, most of the roughly 76 million annual cases of food-borne illness are not reported, and most reported cases are not investigated.

A version of this post initially appeared on the Practice Fusion blog.

In the last 2 years alone, Big Pharma has cut its sales force by 10% to 92,000 and some experts predict the number could drop by another 15,000 in the next 2 years.

That will save $3.6 billion for the pharmaceutical companies, who know all too well that results from the investment it has made in its sales force are way down.

In fact, just 37% of drug reps who visit physician offices are able to place drug products in the sample drawer, and a only 20% speak directly with a physician.

Nearly a quarter of all physicians practice within a group that bans reps altogether.

That one reason why Big Pharma has become so excited about ePromotion, a term encompassing 3 relatively new techniques by which drug manufacturers can doctors about their products, even in the absence of Sid the Drug Rep.

The ePromotion troika includes virtual details, which include video and audiotapes, text messages and email (but no live communication), video details, which include live chat or telephone-assisted Internet sessions in which physicians can speak directly with a representative, and virtual events which include CME events, webinars, conference calls and panel discussions.

Big Pharma’s enthusiasm will likely grow as it digests the results of a new survey showing that doctors’ attitudes toward ePromotion are becoming increasingly positive.

SDIHealth concluded this after completing its Annual Study of ePromotion, the 8th such iteration of the poll.

The Study revealed that 67% of physicians expressed a positive attitude toward ePromotion, up 5% from the previous year.

73% of the surveyed physicians felt ePromotion was at least as effective as face-to-face promotion by drug reps, a jump from 68% the year before.

 The average time spent per doctor, per ePromotion activity was a robust 18 minutes.

With each year, “we have seen acceptance toward ePromotion among physicians increase,” said Jason Fox, Associate Director at SDI.

“The results of this survey underscore a growing opportunity for the two groups to interact more regularly.”

Steven Forage, a metro-DC-based software salesman spends 5 hours per day behind the wheel. Like so many others, he’s closing deals on his cell, drinking coffee and checking email, in addition to driving.

One thing he worries about no more, however, is getting nailed by a speed camera.

That’s because Forage tricked-out his Caddy with PhantomAlert, a system that links all known locations of the cameras with his GPS and warns him when he’s approaching one.

“Fuzz alert!” shouts an electronic voice from his dashboard. “Ding, ding. Ding, ding. Fuzz alert!”

PhantomAlert has subscribers all over the country, including more than 2,000 in metro-DC alone according to it’s owner, Joseph Scott.

Scott’s employees access the locations of speed cameras from government and police Web sites, and receive tips from subscribers as well.

Scott believes cops should dig his device, since after all the cameras are there to slow-down drivers and not generate cash from tickets. “Not only should they support us,” Scott told the Washington Post, “but when they mail out citations, on the back they should say, ‘Get PhantomAlert.’ “

Some officials disagree. “If drivers think they only get a ticket when their little device goes off, that could lead them into a false sense of security, which could cause them to speed,” Lisa Sutter, a District employee who runs camera enforcement operations in DC told the Post.

But in fact others see merit in Scott’s device. Corinne Geller, a spokeswoman for the Virginia State Police, thinks PhantomAlert could create a perception that there is more surveillance going on at any time than is actually the case. “If it’s a deterrent, that’s a good thing,” Geller said.

A version of this post originally appeared in the Practice Fusion Blog.

The US Department of Veterans Affairs will allow clinical investigators to use de-identified patient information contained in its EMR as a means to support clinical research initiatives on subjects ranging from MRSA to posttraumatic stress disorder, heart failure and cancer.

Matthew Samore, an epidemiologist from the VA Salt Lake City will be involved with the project. He opined that the so-called Consortium for Healthcare Informatics Research “will not only inform new guidelines but help resolve some conflicts in current guidelines.”

Only VA-associated investigators will get the keys to the highway.

Samore said he hoped the project would show how data-mining techniques could be used in other EMR systems, but worried that since most EMR systems are so poorly interoperable, it would be quite some time before they could match the VA’s capabilities in this area.

Pam Matthews, a senior director of health care information systems at HIMSS concurred with this prediction. “The VA is a closed system. When you apply (what they are doing) to the commercially available products, their data model, their software model may be different,” she said to AMedNews.

Web-based EMRs eliminate these problems, however, by securely storing patient records in a central repository that is continually available to all health professionals involved with the care of a particular patient. 

The VA begins its initiative under a dark cloud caused by the heist of a laptop containing data on 26 million vets, a bit of a privacy issue that is avoided with Web-based solutions since the data are housed in secure, off-site locations.