Drug data reveal sneaky side effects:
An algorithm designed by US scientists to trawl through a plethora of drug interactions has yielded thousands of previously unknown side effects caused by taking drugs in combination. The work, published today in Science Translational Medicine1, provides a way to sort through the hundreds of thousands of 'adverse events' reported to the US Food and Drug Administration (FDA) each year. “It’s a step in the direction of a complete catalogue of drug–drug interactions,” says the study's lead author, Russ Altman, a bioengineer at Stanford University in California. Pills in pill boxes. A program predicts the potential side-effects of mixing different pills. Although clinical trials are often designed to assess the safety of a drug in addition to how well it works, the size of the trials needed to detect the full range of drug interactions would surpass even the large, late-stage clinical trials sometimes required for drug approval. Furthermore, clinical trials are often done in controlled settings, using carefully defined criteria to determine which patients are eligible for enrollment — including other conditions they might have and which medicines they can take alongside the trial drug. Once a drug hits the market, however, things can get messy as unknown side-effects pop up. And that’s where Altman’s algorithm comes in. “Even if you show a drug is safe in a clinical trial, that doesn’t mean it’s going to be safe in the real world,” says Paul Watkins, director of the Hamner–University of North Carolina Institute for Drug Safety Sciences in Research Triangle Park, North Carolina, who was not involved in the work. “This approach is addressing a better way to rapidly assess a drug’s safety in the real world once it is approved.”
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Altman and his colleagues have been studying drug–drug interactions as a way to understand how a person’s genes influence their response to pharmaceuticals. To do that, he says, you must first have a good picture of the molecular mechanisms that underlie drug responses. “Adverse events are incredibly valuable clues to what these drugs are doing in the body,” Altman says. “They can tell you the other pathways in the cell that are being tickled by these drugs.” But reports of adverse drug events are notoriously prone to bias. For example, cholesterol-lowering treatments are more often taken by older patients, and so conditions associated with ageing, such as heart attack, could be wrongly linked to a drug as a side effect. Altman and his colleagues reduced this bias by adopting an approach sometimes used in observational clinical trials. They developed an algorithm that would match data from each drug-exposed patient to a nonexposed control patient with the same condition. The approach automatically corrected for several known sources of bias, including those linked to gender, age and disease1. The team then used this method to compile a database of 1,332 drugs and possible side effects that were not listed on the labels of those drugs. The algorithm came up with an average of 329 previously unknown adverse events for each drug — far surpassing the average of 69 side effects listed on most drug labels. The team also compiled a similar database looking at interactions between pairs of drugs, which yielded many more possible side effects than could be attributed to either drug alone. When the data were broken down by drug class, the most striking effect was seen when diuretics called thiazides, often prescribed to treat high blood pressure and edema, were used in combination with a class of drugs called selective serotonin reuptake inhibitors, used to treat depression. Compared with people who used either drug alone, patients who used both drugs were significantly more likely to experience a heart condition known as prolonged QT, which is associated with an increased risk of irregular heartbeats and sudden death. A search of electronic medical records from Stanford University Hospital confirmed the relationship between these two drug classes, revealing at roughly 1.5-fold increase in the likelihood of prolonged QT when the drugs were combined, compared to when either drug was taken alone. Altman says that the next step will be to test this finding further, possibly by conducting a clinical trial in which patients are given both drugs and then monitored for prolonged QT. What should the drug regulators do with the thousands of possible side effects Altman and his team uncovered? That is a complex problem, says Watkins, who adds that regulators will have to factor in the availability of alternative treatments and the magnitude and seriousness of the side effect, among other considerations. Altman, who serves as an adviser on the FDA’s Science Board, says that he plans to present his results to the agency. He suggests that the algorithm could be used with the FDA’s existing drug-surveillance programs to remove bias. However, he points out the enormity of the task: “We’ve just released a database with 10,000 or more adverse events,” he says. “I do not expect the FDA to uncritically take these results and add them to every drug label.”
Authorities find remains of 167 people in southern Mexico:
Authorities have found the remains of 167 people, believed to be at least 50 years old, in the southern Mexican state of Chiapas, officials said. The remains were discovered inside a cave on the Nuevo Ojo de Agua ranch, and show no visible signs of violence, according to a statement from state prosecutors Studies will be done to determine the age, sex and cause of death of each person, it read. The prosecutors promised not to rule out "any line of investigation." Though the remains are thought to be more than half a century old, the discovery is still sure to attract attention in a country where mass graves have been unearthed in recent years. The bodies of 72 migrants from Central and South America were discovered at a ranch in northern Mexico in August 2010. In the same area, authorities found mass graves last year, containing the remains of nearly 200 people. They began finding the graves while investigating the kidnappings of bus passengers.
U.S. Government Now Creating Terrorists So It Can Arrest Them:
Mohamed Osman Mohamud, a 19-year-old U.S. citizen, was arrested this weekend for plotting to detonate a bombat a downtown Portland, Oregon tree-lighting celebration. So that’s good, right? Americans appreciate not getting blown up. But the thing is, Mohamud was never a member of a terrorist group. The FBI provided him a fake bomb and worked with him in the planning of the attack. But that’s not unusual these days, because the government no longer just tries to find and arrest actual terrorists; it also tries to create terrorists it can then arrest. In fact, informants now like to stand in the parking lots of American mosques, offering hundreds of thousands of dollars and fancy cars to anyone who will sign up for jihad. It’s a brave new world for thoughtcrime. Mohamud was a student at Oregon State, and as far as we can tell from this AP story, was not promised to get rich quickly by becoming a terrorist. He, at least, did have an actual interest in becoming one, because the FBI saw his e-mails to a friend in Pakistan, asking if he knew Osama bin Laden’s AIM handle or whatever. When Mohamud had no luck getting this contact info (WHAT? HIS FRIEND WAS IN PAKISTAN! HE MUST HAVE KNOWN TERRORISTS!), the government swooped in and told him they were hip terrorist guys with a bomb and a terrorist letterman’s-jacket with his name stitched on it. Oh, why was the FBI reading this Mohamud guy’s e-mails in the first place? It’s never explained in this AP story. But c’mon, the kid’s name is Mohamud. He shouldn’t have let his parents name him that if he didn’t want to be a terrorist. So obviously the answer to this problem was not continued surveillance but rather to entice this kid into dropping out of college to become the ULTIMATE TERRORIST. It was also very difficult to decipher that this kid is an American citizen, because the AP story was so busy telling us he is a “Somali-born teenager” and PRECIOUS SMALL WHITE CHILDREN were at this Portland Christmas event (at which they were never in danger of exploding). But here’s an even more fun account in Slate about “four African-American ex-cons from Newburgh, N.Y.” who were enticed into saying they would blow up two synagogues:
Hussain bought meals for the group of four men he assembled because none of them had jobs or money. The owner of a Newburgh restaurant where they occasionally ate considered him “the boss,” because he would pick up the tab. Among his other inducements were the offer of $250,000 and a BMW to the most volubly anti-Semitic plotter, the man the government says was the ringleader, James Cromitie. To drive that car, Cromitie would have needed a driver’s license—which he didn’t have. Another supposed plotter, a Haitian, was a paranoid schizophrenic (according to his imam), which was the reason his deportation had been deferred (according to The Nation’s TomDispatch.com), and who kept bottles of urine in his squalid apartment (according to the New York Times). The last two, both surnamed Williams, have histories of drug busts and minimum-wage jobs in Newburgh. At trial the government asserted that the plot was driven by anti-American hatred. But in papers filed in court by defense lawyers before the trial began, Cromitie is quoted in government transcripts explaining to Hussain that the men “will do it for the money. … They’re not even thinking about the cause.”
One of these guys tried to back out, “saying he didn’t want to hurt any women or children,” but the informant pressured him into staying with the group. This is just perverse. Perhaps the government will one day figure out how to wind down bureaucracies and bureaucratic divisions once they’re proved no longer necessary. But until then, the FBI will create terrorists for itself to bust because it doesn’t have enough actual, group-aligned terrorists to hunt. And, perhaps, a fake bomb for you to assemble will suddenly arrive on your doorstep one day after you criticize the government or American society. But anti-terrorism efforts have to adjust to the actual threat eventually, right? It’s not like archaic bureaucracies like the Tennessee Valley Authority are still around.
Mohamud was known at the Salman Al-Farisi Center in Corvallis, said Yosof Wanly, imam at the mosque. He said Mohamud was “an average university boy,” drinking the occasional beer with friends in fraternities.
“He had some fraternity friends,” Wanly said. “He would attend athletic (events), basketball games, whatever they are.”
By the way, you know who coaches that basketball team? Known terrorist Barack Obama’s brother-in-law. DUN DUN DUN
