When a US embassy employee in East Asia clicked on an e-mail attachment in May, 2006, she inadvertently unleashed the largest cyberattack ever launched against the State Department. The breach permitted China-based attackers to insert malicious computer code into the department’s networks throughout the region.

A cyber-threat response team leapt into action and toiled 24/7 for 2 weeks to isolate the code and develop a patch that officials claim prevented a gargantuan breach.

Unfortunately, State is better equipped to handle cyberattacks than other parts of the federal government. And 2 months later, the Bureau of Industry and Security, a part of the Commerce Department that oversees exports of technology that has both commercial and military uses, was attacked in similar fashion.

The attack was not recognized for days and Commerce was never able to determine when the initial intrusion took place (Commerce claims there is no evidence data was compromised as a result).

Commerce and other parts of government are trying to improve their performance in this regard, but their efforts are often stymied by a marked shortage of skilled computer-security workers, from front-line technicians to so called Security Generals. 

Meanwhile, according to the Government Accountability Office, the number of probes, scans and attacks reported to the Homeland Security Department’s Computer Emergency Readiness Team more than tripled between 2006 and 2008, from 5,500 to 16,840.

The manpower shortage is impacting Pentagon efforts to staff-up a new Cyber Command and Homeland Security’s plans to increase it’s cyber-staff by 1,000 people over in the next 3 years.

The intense demand has sparked bidding wars among agencies and contractors for a small pool of special talent: skilled technicians with security clearances. Some young people with 3 years’ experience and a clearance are commanding salaries over $100,000. 

Philip Reitinger, deputy undersecretary of Homeland Security’s National Protection and Programs Directorate, conceded he couldn’t match private sector pay scales. “But in government,” he told the Washington Post, “one can have a bigger ability to effect change at an earlier place in your career than anywhere else.” he said.

Besides, Reitinger added, “your country needs you.”

MannKind Corporation recently accounced that it has encountered a disappointing setback in its efforts to bring Afrezza to market. The FDA, it turns out, wasn’t able to sign-off on the company’s new drug application for the ultra rapid-acting form of inhaled insulin by January 16, the date the FDA had previously set for itself as a deadline for making this decision.

Apparently, the FDA has not completed inspecting the insulin manufacturing facilities of N.V. Organon, a third-party supplier to MannKind.

The FDA “must complete this inspection before it can finalize its review of our NDA,” said Alfred Mann, Chairman and CEO of MannKind. “To our knowledge, all other FDA inspections are complete. There are no pending answers to any FDA questions or other deliverables due on MannKind’s part.”

The FDA did not set a new date for completing the NDA.

Just one week before the FDA’s surprising announcement, Mannkind had suggested that FDA approval was in the bag.

According to Pharmalot, Mann has bet nearly half of his $2 billion fortune on Afrezza. Many competitors have given up on inhaled insulin products since Pfizer’s fiasco with a similar product, Exubera.

Some analysts were skeptical about the prospects for Afrezza in light of the recent surprise. For example, Hapoalim Securities’ Jon LeCroy said, “the fact that there is now no definite time-line for approval (is) a major negative, as drugs that have a missed PDUFA often take months to years to receive a final decision.”

However, Simos Simeonidis at Rodman & Renshaw believes there is a 75% chance the FDA will approve the drug this year.

Afrezza achieves peak insulin levels within 12-14 minutes of administration, which mimics the release of meal-time insulin in healthy individuals.

Running in commercially-available athletic footware puts more stress on the hip, knee and ankle joints than running barefoot, according to a new study. In fact, a good jog in those designer statements puts more stress on your joints than a walk in high-heeled shoes.
 
To determine the effect of modern-day running shoes on lower extremity joint torques during running, D. Casey Kerrigan and colleagues from JKM Technologies and the University of Virginia recruited 68 healthy young adult runners (37 women) that used commercially-available running shoes.
Subjects had no history of musculoskeletal injury and ran at least 15 miles per week.

Running shoes with typical design characteristics were provided to all subjects. The subjects ran barefoot and with the shoes. Running speed was controlled by the scientists.

Kerrigan’s team analyzed their subjects’ strides using three-dimensional motion capture and ground reaction force with a tricked-out treadmill.
 
The team found that running shoes increased joint torques at the hip, knee and ankle compared with bare feet. In fact, the shoes were associated with a 54% increase in hip internal rotation torque, a 36% increase in knee flexion torque, and a 38% increase in knee varus torque.

The team also found that running shoes caused pronounced stress at anatomical sites of the knee that are prone to the development of osteoarthritis.

They speculated that their findings were caused by the elevated heel and the padding under the medial arch which are typical of modern running shoes. They also acknowledge that running shoes provide good support and protection for the foot itself.

Reducing joint torques with footwear to that of barefoot running, while providing meaningful footwear functions should be the goal of new footwear designs,” the authors wrote.

The write-up appears in PM&R.

You may or may not know by reading the label.

Nearly 20% of the 84,000 chemicals being used commercially in the US—from rust removers to driveway sealants—are being legally kept secret from the public, according to the Environmental Protection Agency.

That gaping problem arose after Congress passed the Toxic Substances Control Act in 1976 to help protect trade secrets but made it rather easy for manufacturers to bypass normal regulatory scrutiny, even when it involves chemicals that could pose harm to humans.

Nearly 95% of the notices for new chemicals received by the Feds in recent years requested the silent treatment. Roughly 700 chemicals are introduced each year to the American market.

Of the nearly 17,000 secret chemicals, most are probably harmless. But chemical producers have disclosed in mandatory reports to the Feds that many pose a “substantial risk” to public health or the environment.

In March, for example, over half of the 65 “substantial risk” reports received by the EPA involved secret chemicals.

151 of the secret chemicals are made in quantities equal to or greater than 1 million tons per year. Ten of them are used in products designed for children, the EPA reports.

Select EPA employees do know the identities of the secret chemicals but they are prohibited from sharing the information with other federal or state officials, emergency responders and the public.

“Even acknowledging what chemical is used or what is made at what facility could convey important information to competitors, and they can start to put the pieces together,” Mike Walls, vice president of the American Chemistry Council told the Washington Post.

The Obama administration wants Congress to make manufacturers prove a chemical should be kept confidential, and wants to allow EPA officials to share that confidential information with state regulators who implement most EPA mandates across the country. Stay tuned.

An expert panel has advised the Food and Drug Administration to green light Crestor, AstraZeneca’s cholesterol-buster, for a wider role in the prevention of cardiovascular disease. FDA acceptance of the panel’s recommendations could markedly increase utilization of Crestor and drugs like it.

The recommendation follows release of data from the so-called Jupiter trial, which was sponsored by AZ. In Jupiter, Crestor reduced the risk of heart attacks in apparently healthy adults with no prior history of cardiac disease and normal cholesterol levels.

Participants in Jupiter did have elevated levels of C-reactive protein (CRP), a non-specific marker for inflammation that identifies people at risk for cardiac events regardless of their cholesterol levels.

Jupiter participants who took Crestor experienced a 54% reduction in the risk of heart attack and a 48% reduction in the risk of stroke. They were 46% less likely to require angioplasty or coronary bypass surgery and had 20% lower mortality from all causes.

In reaching its decision, the expert panel noted that Crestor patients developed diabetes at a higher rate than the placebo group, and experienced more deaths due to GI disease and more episodes of mental confusion. But the panel felt these events were due to chance rather than Crestor itself.

AZ wants the FDA to authorize a discussion of the Jupiter study on Crestor’s label, since this would permit the company to market Crestor to a much wider patient population.

Crestor already generates $3.6 billion in annual revenues for AZ, which is good for 9% of the US market. Pfizer’s Lipitor (27%) and generic statins (49%) have the lion’s share of this market.

Both Lipitor and the generic simvastatin have been shown to lower CRP levels. It is estimated that the label modifications would apply to about 6 million US patients.

Plavix, the clot-busting blockbuster marketed by BMS and Sanofi, is never out of the news for long.

One story that developed legs in the last year for example, was the finding of apparent marked variability in responsiveness to the drug. This begat calls for personalized prescribing of Plavix based on genetic markers, and warnings that Nexium-The Purple Pill—impaired its effectiveness, thus creating an increased risk of vascular complications.

Now it seems, the worm has turned again on this story. Victor Serebruany and colleagues have reported that the issue of Plavix nonresponsiveness may be caused by something rather mundane: non-compliance with the drug.

To reach this conclusion, the scientists obtained blood samples from 422 heart disease patients and 209 poststroke patients that had platelet activity tests performed before and after Plavix use.

They tested these archived blood specimens for a chemically stable, carboxyl metabolite of Plavix, and then defined Plavix noncompliance to be a very low plasma concentration of this inactive metabolite.

They found that 138 patients (22%) were in fact noncompliant. Noncompliance was more frequent in stroke victims (38%) than cardiac disease patients (14%).

“Some of the patients whom we would classically describe as ‘resistant’ to clopidogrel, in that they showed low levels of platelet inhibition, in fact didn’t actually have clopidogrel on board,” Serebruany told Medscape.

“The whole variability issue with clopidogrel (Plavix) is not such a big deal,” Serebruany added. “It has been hyped by the manufacturers of the newer antiplatelet agents. If we did studies with these agents, they would show variability, too.”

“Future antiplatelet trials should recognize noncompliance as a critical confounding factor, and every attempt should be made to minimize and strictly monitor prescribed antiplatelet regimens,” the authors concluded.

How’s this for a cool high-school science project?

Brenda Tan and Matt Cost, a pair of students at Trinity High School in Manhattan, recently performed DNA analysis of food items and other objects collected in their homes and surrounding environs.

They found a hellacious mix of mislabeled and possibly tainted food items and raised a ton of questions in the process.

Among their notable discoveries:
-  A pricey chunk of so-called sheep’s milk cheese turned out to have been derived from cow’s milk,
-  Fish labeled smelt turned out to be Japanese anchovy,
-  “Venison” dog treats were actually made from beef
-  Sturgeon caviar samples contained DNA from that widely-known delicacy, the Mississippi paddlefish.

The students dubbed their project “DNAHouse.” They analyzed their collections using the Barcode of Life Database which is normally used in species identification. They secured help from DNA barcoding experts at Rockefeller University and the American Museum of Natural History for their project.

A write-up of their work appears here.

“We do not know where or why the mislabeling occurred, but most cases appeared to involve substitution of a less expensive or less desirable item, suggesting the possibility of deliberate mislabeling for economic gain,” the authors wrote. “We also think mislabeling is a serious problem because certain individuals have allergies or dietary restrictions regarding certain foods.”

Trinity has a track record for producing these kinds of stories. Last year, 2 other Trinity students created a stir by reporting that one-quarter of the fish at local markets and restaurants was mislabeled.

Of note, Tan and Cost also sampled hair from several classmates. “We were happy to report,” they wrote, “that our classmates came back as 100% human.”

More than half of American adults, 54%, drink coffee regularly. They consume nearly 400 million cups of it each day making its active ingredient, caffeine, by far the most widely consumed drug in the country.

So you’d think we’d have reached some general agreement on how the stuff affects our health by this time, no?

Alas, that’s not the case.

Recent studies of the matter  suggest that coffee has beneficial effects on health. Last month for example, scientists reported that people who consumed 3-4 cups of Joe per day developed Type 2 diabetes 25% less frequently than those who had less than 2 cups per day.

Another group recently reported that men who drank at least six cups per day developed advanced prostate cancer 60% less often than abstainers.

Earlier studies had, in addition, linked coffee consumption to a reduced risk of colon cancer, head and neck cancer, endometrial cancer, cavities, gallstones, Parkinson’s disease, cirrhosis of the liver and Alzheimer’s disease.

On the other hand, many studies show that coffee, and caffeine in particular, raises heart rate and blood pressure as well as homocysteine levels in the blood. The latter is an amino acid that has been associated with stroke and heart disease.  Other studies have linked caffeine to bone loss in elderly women and shown that pregnant women who consume 2 or more cups per day have higher rates of miscarriages and low birth-weight babies.

What explains the confusion? It’s certainly possible that coffee has protean effects on the human body, and a mixed bag of health outcomes. After all, many drugs fall into that category. Another possible reason is that most studies of coffee’s health effects (including the 2 recent ones mentioned above) feature an observational trial design, in which scientists troll large data sets for associations between behavior and health outcomes, without a particular hypothesis in mind at the onset. Read the rest of this entry »

Ever wonder how safe and reliable Granny’s new pacemaker is? In most cases it turns out nobody really knows, because the quality of the evidence used by the FDA to approve these devices is poor, according to a study published in JAMA last week.

Sanket Dhruva and colleagues from UCSF drew these conclusions after examining the premarket approval process (PMA) for 78 high-risk cardiovascular devices that received FDA approval between January 2000 and December 2007.

PMA is the most stringent FDA review process for medical devices. The scientists found that 65% of the PMA applications for devices were supported by exactly one study.

And overall, the quality of the studies was abysmal. Some failed to provide details like the number of enrolled participants. Only 27% of them were randomized and even less, 14%, were blinded (blinded, randomized, controlled trials represent state-of-the-art scientific research).

The scientists concluded that in general, the FDA’s premarket approval process for cardiovascular devices lacked statistical firepower required to control for bias and hence draw valid conclusions.

The scientists understood that it is more difficult to subject medical devices to blinded studies, since there is no way to produce a “sugar pill” (that is, placebo) for medical devices.

“But we were surprised that so many devices were approved on the basis of a single study,” Dhruva told the Los Angeles Times.

The FDA started approving medical devices in 1976. Recently, there has been a marked increase in the number of cardiovascular devices implanted in Americans.  In 2008, 1.2 million people received stents in the US alone. 350,000 people received pacemakers and 140,000 received implantable cardioverter-defibrillators.

Last month, 7 CIA operatives stationed at a forward operating base in the mountains of Afghanistan were blown up by a suicide bomber. Among other things, the tragedy highlighted the CIA’s transformation into a paramilitary organization that operates on the front-lines of America’s war on terror.

The dead operatives had been begun a campaign against a radical nut job known as Sirajuddin Haqqani and his woefully enslaved followers. This crew has claimed responsibility for killing dozens of US soldiers.

In the past year, the CIA has amassed dozens of forward operating bases like this in eastern and southern Afghanistan. In so doing, it has exposed its operatives to enormous risk.

In the 1983 Beirut car bombing, remember, it took a car bomb loaded with 2,000 pounds of explosives to kill eight CIA officers who were based at the heavily fortified American Embassy. All it took this time was one guy dressed in loose-fitting Afghan army fatigues.

These remote outposts are just one feature of the newly militarized CIA. The clandestine agency also uses unmanned drone attack aircraft to pin down and kill nut jobs in Pakistan, and has many operatives in Yemen, home of Umar Farouk AbdulMutallab, the notorious testicle bomber.

According to the New York Times, the CIA has long-since maintained a paramilitary branch known as the Special Activities Division. But the branch was small and rarely used.

Things changed after 9/11 however, when President George W. Bush expanded the agency’s purview to include the capture and/or killing of al Qaeda operatives. The new responsibilities were assigned to Special Activities, which deftly moves and out of countries where the US military can’t operate legally.

The CIA’s expanded mission has included at various times activities such as running a war in Pakistan, organizing secret jails where terrorist suspects could be interrogated, and running an assassination program that once outsourced sensitive operations to Blackwater, a privately-held security company.

President Obama shut down the prisons and called off the dogs, literally, when it came to interrogating terrorism suspects, but green lighted the CIA’s drone program.

Sanofi-Aventis has announced plans to acquire Chattem, maker of popular consumer products like Icy Hot pain reliever and Selsun Blue dandruff shampoo.

The $1.9 billion buy would be the second consumer-focused company purchased by the Paris-based drug giant in less than a year. The other one was France’s Laboratoire Oenobiol, which makes health and beauty supplements and nutritional products.

The moves should help Sanofi diversify beyond prescription drug revenue, which seems like a good idea since its 4 big drugs, Lovenox, Plavix, Ambien CR and Eloxatine will all face generic competition soon.

To accelerate its move into consumer health, Sanofi plans to release an OTC version of Allegra, its allergy drug, which has begun losing market share to Teva’s generic competitor. 
 
Even before the acquisition of Chattem and with little presence in the US consumer products market, Sanofi  managed to generate about $2 billion per year in world-wide OTC sales.
 
“The acquisition of Chattem (gives us) the ideal platform in the US consumer healthcare market,” Chris Viehbacher, CEO of Sanofi told BurrillReport. “Our ability to convert prescription medicines to OTC products will be enhanced by Chattem’s sales, marketing and distribution channels.”
 
Sanofi’s offered Chattem $93.50 per share, a 34% premium. The companies said the transaction should close in Q1, 2010. The deal would make Sanofi the fifth-largest consumer healthcare company in the world as measured by product revenues.
 
Sanofi was notably acquisitive in 2009. In addition to the purchase of Laboratoire Oenobiol, it bought BiPar Sciences and Fovea Pharmaceuticals, and a majority stake in a Russian insulin maker. Sanofi also acquired rights to an anti-MRSA vaccine produced by Syntiron and formed a research alliance with Cal Tech.

Inhibiting an enzyme known as Sirt1 in a particular region of the brain helps reduce food intake, according to scientists at Brown University. The discovery could open the door to new pharmacologic options for the management of obesity.

Sirt1 is found in many tissues including the liver and pancreas.

Earlier studies had shown that Sirt 1 had a fundamental role in cell differentiation, aging and death.

In these studies, both fasting and the antioxidant compound resveratrol-which is found in red wine–activated Sirt1 in peripheral tissues. This phenomenon was associated with improved exercise capacity, improved glucose control and prolonged survival in rats.

The Brown study, conducted by Eduardo Nillni and colleagues, is the first to study Sirt1 activity in the hypothalamus, a region of the brain known to be associated with appetite. 

Nillni’s team used 2 methods to inhibit hypothalamic Sirt1 activity: pharmacological inhibition and RNA transcription blockade. Both approaches resulted in reduced food intake and weight loss.

The scientists also found that fasting increases hypothalamic expression of the Sirt1 gene, which makes it even more likely that Sirt1 plays a central role in moderating appetite and hunger in mammals.

Nillni now plans to study how obesity affects Sirt1 activity in the brain.

The write-up is in PloS One.

Medicare has stopped paying claims to Miami-based Fernando Mendez-Villamil, MD, until it can figure out whether his prolific prescription writing is legit. The psychiatrist has written 96,685 prescriptions to Medicaid patients over the last 21 months.

That works out to an astonishing clip of 150 prescriptions per day, 7-days per week. It is nearly twice as many as the runner-up prescriber, Huberto Merayo, whose office is just a few blocks from the Prescription King.

In fact, the top 7 prescribers of mental-health drugs in the state all reside in the Miami-Dade area.

According to the Miami Herald, Miami-Dade is at or near the top, depending on the measure, of the most expensive places to get health care in the nation.

“While the state is investigating, we haven’t paid his claims,” Medicare spokesman Peter Ashkenaz told the Herald. Apparently, Medicare cut off the spigot last May.

The story hit the press after Charles Grassley, a Republican Senator from Iowa released a letter he had written to Medicare and Medicaid officials in which he inquired about their procedures for detecting over-utilization of medical services. The letter didn’t mention Mendez-Villamil by name, but did cite the number of prescriptions he had written.

The Herald used the astronomical number to trace the allegation back to Mendez-Villamil.

The psychiatrist told The Herald that he prescribes only drugs that are medically necessary, that he works long hours, averages 10 minutes per patient visit, and many of his patients are taking 4 or 5 drugs.

Grassley’s letter, it should be noted, concerned only Medicaid prescriptions. No one seems to know how many scripts the prolific psychiatrist penned for patients covered by Medicare.

It’s been a week since Google announced its Gmail systems had been breached by cyber criminals based in China, but the scope of the attack is just now being appreciated.

It looks as though the attack was part of a large corporate and political phishing ploy that leveraged security flaws in e-mail attachments to break into the networks of at least 34 companies including  Yahoo, Symantec, Rackspace, Adobe and Northrop Grumman.

According to Google, the hackers accessed the Gmail accounts of Chinese human rights advocates around the world, as well as other human rights groups that shape the national debate on human rights in China.
 
Google has threatened to retaliate by pulling out of China altogether.

The attacks were more sophisticated than their predecessors, according to security experts, in that they simultaneously exploited flaws in many software programs.

“Usually it’s a group using one type of malicious code per target,” Eli Jellenc told the Washington Post. Jellenc, the head of international cyber-intelligence for VeriSign’s iDefense Labs, added that “in this case, they’re using multiple types against multiple targets. That’s a marked leap in coordination.”

The standoff between Google and China creates a headache for federal officials, since it cuts to the heart of many current issues in U.S.-China relations: from human rights and censorship to intellectual property protection and access to military technology.

Since it entered the Chinese market in 2005, Google has clashed with the Chinese government about which search topics should be censored. The company’s service has been blocked when it defied government wishes.

News about Google’s public rebuke was censored in China, other than an op-ed piece in People’s Daily which called the search giant a “spoiled child” and predicted it would eventually back-off its threats.

The health reform “debate” (such as it is) has highlighted our nation’s PCP shortage, but there’s another area where the demand for MD-level services outstrips supply: pediatricians trained in sub-specialties like gastroenterology, rheumatology, and developmental -behavioral medicine.

NACHRI, the National Association of Children’s Hospitals and Related Institutions recently briefed Congress on the matter, in an attempt to favorably influence the “debate.” 

A recent survey of its members, NACHRI officials said, revealed widespread shortages in multiple pediatric specialties which have forced 90% of member’s facilities to delay appointments.

What is more, members reported that vacancies for specialty pediatricians often remained unfilled for more than a year. The most severe shortages are in cardiology, oncology, hematology and developmental-behavioral medicine.

The latter shortage is of particular concern in light of the recent spike in autism-related disorders. Half the members in the survey reported delays of more than 3 months before getting to see a developmental specialist as a result.

Part of the explanation for the shortage is the woefully inadequate compensation these specialists receive. It amounts to just more than half the haul raked in by their counterparts in adult care.

In this regard, a provision in the House bill which requires Medicaid to pay Medicare rates for office visits would really help, NACRI officials say. NACHRI is also lobbying for increased funding for specialty training and a loan-forgiveness program.

In Pediatrics, specialization requires 2 to 3 years of training after the general pediatrics residency is completed. 

“While most of us are driven into this profession because we love kids, the vast majority leave training with huge debt and the prospect of not making very much money at the end,” John McBride told the Wall Street Journal. McBride is a pediatric pulmonologist at Akron’s Children’s Hospital Medical Center.

Pfizer, the world’s largest drugmaker, has announced plans to pursue aggressive sales growth and market-share targets in China. In doing so, it hopes to take advantage of the nation’s unmet needs for health care which have been prompted by an economic boom and an associated increase in diabetes and hypertension.

In a recent interview with the Wall Street Journal, Pfizer’s Regional President of North Asia Allan Gabor said the company wants to increase sales in China by 25% per year.

“When you look at where we are in China today, even though our growth rate is high, the market share is relatively low. And that’s a function of … the nature of the competition here, and the fact that patent law wasn’t really established until 1993,” Gabor told the Journal.

Pfizer is well positioned in the cardiovascular disease market with the blockbusters Lipitor (for cholesterol) and Norvasc (for high blood pressure). Last month, Pfizer rounded out this portfolio by announcing a deal to help Takeda Pharmaceuticals market Actos, a drug for type 2 diabetes, in China.

Pfizer is already the largest foreign pharmaceutical company on the mainland, yet it controls only 2% of the market. The Chinese pharmaceutical market is remarkably fragmented, with thousands of local players in the mix.

The market for pharmaceuticals in China rose 27% last year, and most forecasters believe it will grow by at least 20% per year in the foreseeable future.

Pfizer’s recent acquisition of Wyeth will help. The latter’s pneumococcal vaccine, Prevnar, was “one of the most successful product launches in China history,” Gabor said. Wyeth also adds the popular vitamin supplement Centrum, and baby formula which became popular after last year’s melamine scare.

Pfizer’s move comes about 2 months after Swiss pharmaceutical giant Novartis announced it will invest $1 billion into an R&D facility in Shanghai.