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A Moment to Stop and Remember

Posted on January 29, 2010 by Danzig

I want to pause today with NASA to honor our astronauts who lost their lives furthering the cause of space exploration and discovery. Today, Kennedy Director Bob Cabana will lay a wreath at the Space Mirror Memorial in honor of these brave people… gone too soon. Let us never forget.

On January 27, 1967, Gus Grissom, Ed White, and Roger Chafee were working in the Apollo 1 space capsule atop the launch pad when a fire broke out inside the capsule. Neither the astronauts nor the ground crew were able to open the door to the capsule. Ground crew monitoring communications were forced to listen to these brave men as they tried to escape.

On January 28, 1986, just 73 seconds after launch, a booster engine failed on the Space Shuttle Challenger. As the world watched in horror, we lost seven very special people. We will never forget Francis Scobee, Michael Smith, Judith Resnick, Ellison Onuzuka, Ronald McNair, Gregory Jarvis, and Christa McAuliffe.

On February 1, 2003, with only 16 minutes until landing, Mission Control lost contact with the Space Shuttle Columbia. After a successful mission, Columbia broke up on re-entry, and we lost Rick Husband, William McCool, Michael Anderson, Ilan Ramon, Kalpana Chawla, David Brown, and Laural Clark.

High Flight

Oh! I have slipped the surly bonds of Earth

And danced the skies on laughter-silvered wings;

Sunward I’ve climbed, and joined the tumbling mirth

of sun-split clouds, — and done a hundred things

You have not dreamed of—wheeled and soared and swung

High in the sunlit silence. Hov’ring there,

I’ve chased the shouting wind along, and flung

My eager craft through footless halls of air….

Up, up the long, delirious, burning blue; I’ve topped the wind-swept heights with easy grace; Where never lark nor even eagle flew—; And, while with silent lifting mind I’ve trod; The high untrespassed sanctity of space,; Put out my hand, and touched the face of God.
John Gillespie Magee, Jr.
.
.

Requiescant in pace.

Space Shuttle image by Irish Barren on Photobucket

CSF Statement on NASA’s Anticipated Announcement of a $6 Billion Commercial Crew Program and NASA Budget Increase

Posted on January 29, 2010 by Danzig

Washington, D.C. – The Commercial Spaceflight Federation is issuing the following statement applauding NASA’s anticipated announcement of a $6 billion competitive, commercial crew program and welcoming the President’s show of support for NASA with his significant planned increase for NASA’s overall budget:

Bretton Alexander, President of the Commercial Spaceflight Federation:

“NASA investment in the commercial spaceflight industry is a win-win decision: commercial crew will create thousands of high-tech jobs in the United States, especially in Florida, while reducing the spaceflight gap and preventing us from sending billions to Russia. This is on par with the early days of aviation and the U.S. Airmail Act, which spurred the growth of an entire new industry that now adds billions to the US economy every year.”

“At a time when job creation is the top priority for our nation, a commercial crew program will create more jobs per dollar because it leverages millions in private investment and taps the potential of systems that serve both government and private customers. We have a tremendous opportunity here to jump-start private activity in low-Earth orbit that will further lower the cost of access to space and unleash the economic potential of space long promised.”

“Working with NASA, industry can develop the capabilities to safely launch U.S. astronauts just as commercial spaceflight providers are already trusted by the U.S. government right now to launch multi-billion dollar military satellites, upon which the security of our Nation and lives of our troops overseas depend. Investing $6 billion will fund a full program of multiple winners for commercial crew, so that robust competition in the marketplace can reduce costs and generate innovation. We are excited to see such a significant commitment from the Obama Administration and NASA leadership for pursuing this important initiative for NASA and the nation.”

About the Commercial Spaceflight Federation
The mission of the Commercial Spaceflight Federation (CSF) is to promote the development of commercial human spaceflight, pursue ever higher levels of safety, and share best practices and expertise throughout the industry. CSF member organizations include commercial spaceflight developers, operators, and spaceports. The Commercial Spaceflight Federation is governed by a board of directors, composed of the member companies’ CEO-level officers and entrepreneurs. For more information please visit http://www.commercialspaceflight.org or contact Executive Director John Gedmark at john@commercialspaceflight.org or at 202.349.1121.

SpaceShipTwo – The Newest Enterprise

Posted on January 29, 2010 by Danzig

Building upon the successful 2004 flight of SpaceShipOne, Virgin Galactic and Scaled Composites have rolled-out their latest craft. SpaceShipTwo, the VSS Enterprise (see video), carries six passengers and two pilots. It will be carried to high altitude by the mothership WhiteKnightTwo, the VMS Eve,

NCBI ROFL: Civilian gunshot injuries of the penis: the Miami experience. | Discoblog

Posted on January 29, 2010 by Danzig

gun “OBJECTIVES: To perform a retrospective study to evaluate the circumstances, extent of trauma, and modalities of treatment for penile injuries caused by firearms in a large metropolitan area. The management of civilian injuries differs significantly from that of the military, and experience with penetrating trauma to the external male genitalia in civilian life has been minimally reported. METHODS: From 1989 to 2006, 58 patients with gunshot wounds of the penis were evaluated at Jackson Memorial Hospital in Miami, Florida… … CONCLUSIONS: Gunshot wounds to the penis are rare and are commonly associated with injuries of other organs. In sharp contrast to military injuries, minimal tissue destruction is seen, and minimal debridement is needed. If corporal injuries are suspected, penile exploration is warranted.”

Photo: flickr/Willie Lunchmeat

The Tamiflu Spin

Posted on January 29, 2010 by Danzig

I will start, for those of you who are new to the blog, with two disclaimers.

First, I am an infectious disease doctor. It is a simple job: Me find bug. Me kill bug. Me go home. I spend all day taking care of patients with infections. My income comes from treating and preventing infections. So I must have some sort of bias, the main one being I like to do everything I can to cure my patients.

Second, in 25 years I have, to my knowledge, accepted one thing from a drug company. The Unisin (that’s how I spell it) rep, upon transfer from my hospital, sent me a Fleet enema with a Unisin sticker on it. I show it proudly to all who enter my office. I do not even eat the drug company pizza at conference, and I cannot begin to tell you painful that is.

As we leave (I hope) the H1N1 season and enter seasonal flu season, there has been a flurry of articles, originating in the British Medical Journal , questioning whether oseltamivir is effective in treating influenza. The specific complaint at issue is whether or not oseltamivir prevents secondary complications of influenza like hospitalization and pneumonia. Although you wouldn’t guess that was at issue from the reporting. As always, there is what the data says, what the abstract says, what the conclusion says, and what other people say it says. Reading the medical literature is all about blind men and elephants.

There is, evidently, going to be an investigation by the European Union Council of Europe into whether or not the H1N1 pandemic was faked to sell more oseltamivir. Sigh.

Is oseltamivir effective against flu? Lets start with background. What do I want to know about an antiviral to help determine its efficacy?

I would like a mechanism of action that would prevent replication of the virus. I can’t kill a virus, as I can a bacteria, but at least I can stop if from reproducing.

I would like the antiviral to be effective in the test tube at physiologically achievable concentrations.

I would like the antiviral to be effective in an animal model.

I would like the antiviral to be effective clinically: on challenge studies if ethical and in the real world.

There is the virulence of the organism, and there can be strain to stain variation in the virulence. Some influenza strains are better at spreading or killing than other strains. Everyone seems to have forgotten that when H1N1 started in Mexico it apparently had a horrific mortality rate in hospitalized patients.

” By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%).”

The worry was that there was going to be a repeat of the 1919 influenza pandemic. Fortunately the subsequent mortality rate was much less as it swept the world. H1N1 turned out to be a highly infectious, low virulence strain of flu. This time. But I would still fret that one-day there will be another repeat of the 1919 pandemic. The current bird flu has a 66% mortality rate, but is not spread human to human. Maybe someday it will gain that ability. But at the beginning no one knew what mortality of H1N1 or bird flu was going to be and they prepared accordingly. Of course public health officials are always in a no-win situation. They are either going to over-prepare or under-prepare, and as a result at best look a fool and at worst look evil. Next time they may err on the side of under-preparing so they are not accused of faking a pandemic.

There is the hosts ability to respond to the infection. Just as there is variability in the virulence of the pathogen, there is variability in the hosts ability to control the infection. It is often the case that whether you live or die from an infection may be due to the immune system with which you are born. Pubmed ‘toll like receptor’ ‘polymorphism’ and ‘infection’ for further information that is beyond the scope of this entry. There may be an inherited predisposition to dying from influenza.

In the H1N1 pandemic, mild as it was overall, caused disproportionately relatively high mortality in children

“Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) “

and pregnant women

“Data were reported for 94 pregnant women, 8 postpartum women, and 137 nonpregnant women of reproductive age who were hospitalized with 2009 H1N1 influenza… In all, 18 pregnant women and 4 postpartum women (total, 22 of 102 [22%]) required intensive care, and 8 (8%) died.”

Who gets the disease may be, depending on the organism, more important than the strain of infection.

There is how strong or powerful (meaningless terms to an ID doc, but part of the popular language of medicine) the antibiotic is. Antivirals are not that effective because they do not kill viruses, they only halt their replication. Given the prodigious replicative capacity of viruses, it is going to be impossible to shut down every virus from replicating with an antiviral. With HIV it took the combination of three different anti-retrovirals to (almost?) completely shut down viral replication. As those without immune systems prove with depressing regularity, no antibiotic will work for long if the host’s immune system cannot help control the infection.

Finally, there is promptness of therapy. For serious infections even a day in the delay of appropriate antibiotics can dramatically increase mortality. So the later you begin therapy, the less effect one should expect. This is one of the issues with a disease with a very rapid onset like influenza and why the challenge studies, where you give the medication right after exposing the subject to influenza, show better effect. Viral replication will often rapidly outstrip the available antiviral.

What would I expect from an influenza medication?

Prevent disease after exposure?
Decrease the severity of the infection?
Prevent death in all cases? Prevent death in the more severe cases? Decrease the odds of dying?
Decrease complications of the disease?
Some combination of the above?

All good endpoints. As a rule, I expect antivirals for to lessen the severity of disease if given early in the disease.

So what can we say for oseltamivir?

Does it have a mechanism of action that would interfere with viral replication? Yes. Oseltamivir blocks the activity of the viral neuraminidase enzyme, preventing new viral particles from being released by infected cells. Not a thrilling mechanism of action. The virus can multiply all it wants if it infects a cell, and since no drug is 100% effective, one would expect it would slow down the disease, not stop it.
Sometimes, as we shall see, that may be enough to make the difference between life and death.

Does oseltamivir work in the test tube? Yes. In animal models? Yeah. In human clinical trials? Yes.

It is in human clinical trials and the choice of efficacy endpoints where the current brouhaha starts.

LA times headline reads

“British medical journal questions efficacy of Tamiflu for swine flu — or any flu.”

The Atlantic , which has now supplanted the Natural News for the worst medical coverage, has a headline that reads

“The Truth About Tamiflu”

followed by the opening paragraphs.

“Two months ago, we pointed out in our story on flu in The Atlantic that the antiviral drug Tamiflu might not be as effective or safe as many patients, doctors, and governments think. The drug has been widely prescribed since the first cases of H1N1 flu surfaced last spring, and the U.S. government has spent more than $1.5 billion stockpiling it since 2005 as part of the nation’s pandemic preparedness plan.
Now it looks as if our concerns were correct, and the nation may have put more than a billion dollars into the medical equivalent of a mirage. This week, the British medical journal BMJ published a multi-part investigation that confirms that the scientific evidence just isn’t there to show that Tamiflu prevents serious complications, hospitalization, or death in people that have the flu. The BMJ goes further to suggest that Roche, the Swiss company that manufactures and markets Tamiflu, may have misled governments and physicians. In its defense, Roche stated that the company “has never concealed (or had the intention to conceal) any pertinent data.”

The medical equivalent of a mirage. Hmmm. And death? The Cochrane review, upon which the whole controversy revolves, does not comment of prevention of death nor does the BMJ feature or editorial on the topic. Into the second paragraph and already they are apparently making things up. I remember when I trusted the Atlantic. Interestingly, the Atlantic never quotes the results of the Cochran review. They suggest that the review demonstrates that oseltamivir is worthless.

Does it? Start with the methods section.

They looked for randomized, placebo controlled trials. Cochran gold.

“We excluded experimental influenza challenge studies as their generalizability and comparability with field studies is uncertain.”

Which is a shame, as the challenge studies always show efficacy. But they are not representative of the real world as they have the best case for treating with an antiviral: you can start the medication right when the disease may start.

They screened 1416 articles and ended up with 29 studies, 10 for effectiveness, the cream of the crop. 1416 articles is a lot of articles. I know they are not the crème de la crème, and is why I am not a fan on just relying on meta-analysis alone. That is a lot of ignored information. And their results?

Here is the conclusion in the abstract:

“Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomized trials to resolve these uncertainties are needed.”

I am already confused.

“The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective.”

They are effective but they are not. But the abstract suggests in normal people, oseltamivir has modest efficacy.

Later, there is the Take Home message box, which says

“WHAT IS ALREADY KNOWN ON THIS TOPIC
Neuraminidase inhibitors (especially oseltamivir) have become global public health drugs for influenza
They prevent symptoms and shorten the duration of illness by about one day if taken within 48 hours of the onset of symptoms
Toxicity and the effects on complications have been debated
WHAT THIS STUDY ADDS
Neuraminidase inhibitors reduce the symptoms of influenza modestly
Neuraminidase inhibitors reduce the chance of people exposed to influenza developing laboratory confirmed influenza but not influenza-like illness
Evidence for or against their benefit for preventing complications of influenza is insufficient
Evidence for or against serious adverse events is lacking, although oseltamivir causes nausea”

To me the take home message suggests some efficacy. Lets move on to the results and the discussion. Perhaps it will clarify the situation.

“The data suggest that neuraminidase inhibitors are effective at reducing the symptoms of influenza. The evidence is of modest benefit—reduction of illness by about one day. “

Which is what I would expect in a population of healthy, mostly young people with seasonal flu of low virulence.
Note the caveats. Young, healtyh people and influenza of low virulence.
Every season we have new strains of influenza and the ability of influenza to kill people varies from year to year.

“This benefit has been generalized to assume benefits for very ill people in hospital. This seems reasonable, although it is worth remembering that we have no data to support this, and it is unlikely that ethics committees would allow a trial of no treatment for people with influenza who have life threatening disease.”

Yeah. We will probably not have randomized controlled trials in the seriously ill. While we do not have randomized, controlled, clinical trials, we do have data to support the use of oseltamivir in ill patients. Not no data.

In the Mexican experience with H1N1 mentioned above,

“After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8).”

And in pregnant women with H1N1 mentioned above

“As compared with early antiviral treatment (administered 2 days after symptom onset) in pregnant women, later treatment was associated with admission to an intensive care unit (ICU) or death (relative risk, 4.3).”

Or this experience with H1N1

“Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early.”

And what about seasonal flu?

“No randomized trials of neuraminidase-inhibitor treatment of hospitalized influenza patients have been conducted. However, three observational studies suggest that oseltamivir treatment of hospitalized patients with seasonal influenza may reduce mortality. In one prospective Canadian study among hospitalized patients with seasonal influenza, (N=327; mean age, 77 years), in which 71% began oseltamivir treatment >48 hours after illness onset, oseltamivir treatment was significantly associated with a reduced risk of death (OR, 0.21; P=0.03) within 15 days after hospitalization as compared with untreated patients.7 In a subanalysis, in a Hong Kong study of hospitalized seasonal influenza patients (N=356; mean age, 70.2 years), oseltamivir treatment initiated within <96 hours after illness onset was independently associated with decreased mortality as compared with untreated patients (OR, 0.26; P=0.001).8 A retrospective chart review of hospitalized seasonal influenza patients in Thailand (N=445; mean age, 22 years), including 35% with radiographically confirmed pneumonia, reported that any oseltamivir treatment was significantly associated with survival (OR, 0.11; 95% CI, 0.04 – 0.30) as compared with untreated patients.”

In the seriously ill, people who are going to die from influenza, taking oseltamivir appears to decrease the odds of dying. Remember that the authors of the Atlantic article said olsetamivir didn’t prevent death. Maybe their firewall blocks access to Pubmed and Google. Or maybe they are no good at evaluating elephants.

So what would you do if you were in charge of public health policy and confronted with a new strain of influenza, be it H1N1 or bird flu, with a potentially catastrophic mortality rate? Ignore it? Or get as much oseltamivir and vaccine as you could lay your hands on?

Maybe not the highest quality studies, but we have a biologic mechanism, we have test tube and animal studies, we have challenge studies, we retrospective studies that show efficacy. We have a lot of data to support efficacy of antivirals in some patient populations.

The question is not whether oseltamivir is effective, but in what population the medication will be effective and for what strains of influenza. Certainly I am not going to withhold oseltamivir from a hospitalized pregnant female with presumptive H1N1 given an 8% mortality rate. Does a 45 yo with H1N1 or seasonal flu need oseltamivir? No. An 85 year old with multiple medical problems? Probably. Nuance. Subtlety. Understanding the breadth and depth of a topic no longer seems to be part of the Atlantic medical reporting. I originally typed the last sentence as the Atlantis medical reporting. Pity I have to change it; it seemed much more accurate the first time.

The Cochran review states, “Because of the moderate effectiveness of neuraminidase inhibitors, we believe they should not be used in routine control of seasonal influenza.” The first half of statement is a fact, the second half is opinion. The ‘we’ evidently being “Tom Jefferson, researcher, Mark Jones, statistician, Peter Doshi, doctoral student, Chris Del Mar, dean; coordinating editor of Cochrane Acute Respiratory Infections Group.” It is not a ‘we’ that I would use for deciding medical treatment. It is one thing to say that in healthy people from age 14 to 65 treatment is modestly effective, quite another to extrapolate that information to everyone, young and old, healthy and ill, pregnant or not.
If large populations are ill one less day during widespread disease, the positive effects of people returning to school and work can be enormous. Whether olsetamivir is worth the cost and the breeding of resistance requires a complicated cost-effective analysis that I will never understand.

In the Atlantic article they confuse the treatment of seasonal flu in studies in young(er) patients when there is some vaccine immunity and relatively low virulence with preparing for a new pandemic strain with no vaccine, and what appeared at first to be an fearsome mortality rate. In hindsight, now that we know the virulence of H1N1, we did not need to stockpile the oseltamivir for H1N1. If it had continued with the high mortality rate and, based on the studies mentioned above, we would be glad they stockpliled. And if avian flu becomes infectious while maintaining virulence, well, lets just say I am practicing not inhaling for a year.

Does oseltamivir prevent complications? Maybe. But that is not a primary endpoint in treating infections. You want to cure the patient, shorten the illness and prevent death. Oseltamivir does this. If it prevents complications, so much the better, but if it doesn’t I, and my patients, can live with that.

The Atlantic article partly concludes:

“There are a couple of take-home messages here. One is pretty obvious: Tamiflu may not be doing much good for patients with the flu who take it, and it might be causing harm.”

So disingenuous since this is not the conclusion of the Cochrane review. It depends on who you are treating and what strain. It seems that understanding nuance is not part of the Atlantic’s oeuvre. Or even reading the primary sources.

The other part of the Tamiflu kerfuffle is more difficult to discuss because it concerns information we do not have.

As the Cochran review alluded to the fact that they wanted to get original data about the ability of olsetamavir to prevent secondary complications of influenza but the company would not release the information. Note. Secondary complications. Pneumonia increases the risk of heart attack. Treating the pneumonia with penicillin does not prevent the heart attack, but that does not make the treatment of pneumonia less beneficial. Only living people can get a heart attack anyway.

“Attempts to deal with these shortcomings were unsuccessful: although three of five first authors of studies on oseltamivir treatment responded to our contact, none had original data and referred us to the manufacturer (Roche), which was not able to unconditionally provide the information as quickly as we needed it to update this review.”

But the Atlantic was more, well, descriptive

“The dog ate my homework
But when the Cochrane team, led by Chris Del Mar, from Bond University in Australia, re-examined the studies they had previously used in 2006, they found some discrepancies. It turned out that only two of the ten studies had ever been published in medical journals, and those two showed the drug had very little effect on complications compared to a dummy pill, or placebo. So the Cochrane reviewers decided to look at the data for themselves.
First they went to the lead authors of the published studies—the researchers who were supposed to have access to all of the data. One author said he had lost track of the data when he moved offices and the files appeared to have been discarded. The other said he’d never actually seen the data himself, and directed the Cochrane team to go directly to the company.
Four months and multiple requests later, the Cochrane researchers had a hodgepodge of data from the company, including two studies that showed the drug was ineffective, but which the company had never published. Roche also provided data from a third study, which involved 1,447 adults and adolescents aged 13-80, the largest study of the drug ever conducted. Yet the company never published that one either. (A summary of this and other studies is available at http://www.roche-trials.com). But with only partial data, the Cochrane team couldn’t even figure out what the study had been intended to measure.”

That is a problem.

One of things I have learned in blogging and podcasting is how limited and unimpressive meta-analysis and structured reviews are. They do pool the best studies. But often it seems that the process of choosing the studies, much important and relevant information is not considered. Most of infectious diseases is not based on randomized, placebo controlled trials and does not need to be. After reading the influenza Cochrane reviews I am starting to understand the point behind another BMJ meta-analysis. One would have to be a wackaloon at the most bizarre fringes of medicine to demand that I treat endocarditis or meningitis on the basis of such a trial. Other diseases? Not so much.

There is a bit of irony in the whole process. The first Cochrane review of oseltamivir that suggested benefit from oseltamivir was published in 2005.
One would have thought they knew what they were doing since the lead author is touted by the Atlantic as the master of the influenza literature.
Subsequently, a Japanese physician wanted to know more about the details of effect of oseltamivir on complications. Part of the data to demonstrate that oseltamivir is effective is from an article entitled “Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations.” which was a summary of 10 unpublished trials done by the makers of olsetamivir. The review suggested that oseltamivir halved hospitalization.

The Cochrane review, which had used the published data in an earlier meta analysis, decided that they needed to be more rigorous this time. Why they didn’t bother, with their alleged mastery of the literature, to be this rigorous the first time I am uncertain, and it casts a sliver of doubt in my mind as to the rigorousness of the influenza vaccine meta-analysis, so touted in another Atlantic article discussed on this blog.

Turns out Roche tried their best to not release all the data. First they asked for the Cochrane reviewers to sign a non-disclosure contract, then said they were giving the information to another group instead. Why the majority of the studies were unpublished were explained by lame excuses.

“It begged the question: why were so many of the trials still unpublished and not easily accessible?
When the BMJ expressed concern to Roche that eight of 10 treatment trials were unpublished and therefore unverifiable by the general medical community, Roche said that the additional studies “provided little new information and would therefore be unlikely to be accepted for publication by most reputable journals.”
They also added that now it is standard practice for Roche to publish all its clinical trial data, but this was not standard policy within Roche or elsewhere within the industry seven to 10 years ago. “At the time, it was considered that the studies that were published (2 abstracts and 2 full manuscripts) reflected accurately the benefits of the drug,” they said.”

Good questions. Given the history of pharmaceutical companies hiding and obfuscating important data about their drugs, it would be nice if they released the data. Most drug studies are funded by pharmaceutical companies. Does that invalidate the study? No. A drug company study can be just as well done as one funded by an NIH grant. That outcomes will be slightly tilted in favor of the drug if it is funded by the company as compared to non drug company funded studies is recognized. Some studies are well done, some studies are little better than infomercials. In the end you have to read the literature, not the reviews. So I can’t comment on the validity of olsetamivir to prevent complications. Neither can the Cochrane review. Just the Atlantic, who concludes that it is all a mirage. So much sound and fury, signifying nothing.

Then, for each study, there is what the results of the study are, there is the spin put in the discussion, and finally the spin that the drug company reps put on the study when they show it to a doctor.

Kind of like a Cochrane review, huh?

The review says Tamiflu is modestly effective.
Yep.
The conclusion says “Because of the moderate effectiveness of neuraminidase inhibitors, we believe they should not be used in routine control of seasonal influenza.”
Fact, then Spin.
And the drug rep, er, I mean Atlantic says it is nearly worthless.
Lots of unjustified spin.
Remember the conclusion of the review, “Evidence for or against their benefit for preventing complications of influenza is insufficient.”
Pretty mild. The BMJ has an nice discussion on the information, as such as can be determined, from the studies on prevention. By themselves they showed no efficacy but did (may be) when combined. But with no access to the data, there remains uncertainty.

Do drug companies hide and spin important information? Do drug companies inflict bias into studies? Do drug companies influence doctors prescribing habits? Is homeopathy nothing but water?
Yes. It is why you need to consider the entire medical literature.

But to quote the ever helpful Dr. Hill

“All scientific work is incomplete, whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.”

Like evolution, there are multiple lines of evidence to demonstrate oseltamivir efficacy against influenza. When it should be used to get the most bang for the buck depends on the strain of influenza and the patient being treated. And when (not if) we get a pandemic influenza that is both highly infections and highly virulent, I hope we will have a drug like olsetamivir. It will not be a panacea, like penicillin for syphilis. But it will keep some people alive who would otherwise die. The Atlantic concludes

“The more important issue, however, involves the need for trust in science and medicine. Governments, public health agencies, and international bodies such as the World Health Organization, have all based their decisions to recommend and stockpile Tamiflu on studies that had seemed independent, but had in fact been funded by the company and were authored almost entirely by Roche employees or paid academic consultants. So did the Cochrane Collaboration, at least in its earlier assessments of Tamiflu. Millions of flu patients have taken the drug as a result.”

We also need the 4th estate to write and publish quality articles on science and medicine and not go for the easy story of good and bad and obscure importance detail in inflammatory prose. It would be nice if the 4th estate took the time to, oh, maybe actually understand the nuances involved in influenza prevention and treatment. The Atlantic is 0 for 2 with their reporting on influenza. At least I get a topic to write about, and, like their spiritual colleagues Dr. Mercola and The Natural News, the worse the reporting, the better the blog.

New NASA Web Site Launches Kids on Mission to Save Our Planet

Posted on January 29, 2010 by Danzig

NASA’s new "Climate Kids" Web site helps young people understand climate change.

Climate change can be a daunting topic for most adults to grasp, let alone kids. A new NASA Web site can help our future explorers and leaders understand how and why their planet is changing and what they can do to help keep it habitable.

Called "Climate Kids," the new Web site is the latest companion to NASA's award-winning Global Climate Change Web site, http://climate.nasa.gov . Geared toward students in grades 4 through 6, the multimedia-rich Climate Kids site uses age-appropriate language, games and humorous illustrations and animations to help break down the important issue of climate change. Climate Kids can be found at http://climate.nasa.gov/kids .

Visitors to Climate Kids can:

- Command an interactive Climate Time Machine to travel back and forth through time and see how climate changes have affected our world or may affect it in the future.
- Choose the "greenest" transportation options in a game called "Go Green," or go on a "Wild Weather Adventure."
- Learn about green careers from people who are working to understand climate change.

"The climate our children inherit will be different from what we as adults know today," said Diane Fisher of NASA's Jet Propulsion Laboratory, Pasadena, Calif., who developed the content for the site. "Climate Kids aims to answer some of the big questions about global climate change using simple, fun illustrations and language kids can relate to, helping them become better stewards of our fragile planet. Students will learn basic Earth science concepts such as what the difference is between weather and climate, how we know Earth's climate is changing and what the greenhouse effect is."

Climate Kids is a collaboration between JPL's Earth Science Communications Team and NASA's award-winning Space Place website, which is at http://spaceplace.nasa.gov .

NASA's Global Climate Change Web site is devoted to educating the public about Earth's changing climate, providing easy-to-understand information about the causes and effects of climate change and how NASA studies it. For more on NASA's Earth Science Program, visit: http://www.nasa.gov.

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Prometheus: Over Easy

Posted on January 29, 2010 by Danzig

Prometheus displayed its pockmarked, irregular surface for NASA's Cassini spacecraft on Jan. 27, 2010.

Looking for all intents and purposes like a celestial egg after a session in Saturn's skillet, Prometheus displayed its pockmarked, irregular surface for NASA's Cassini spacecraft on Jan. 27, 2010.

Prometheus is one of Saturn's innermost moons. It orbits the gas-giant at a distance of 139,353 kilometers (85,590 miles) and is 86 kilometers (53 miles) across at its widest point. The porous, icy-bodied world was originally discovered by images taken by Voyager 1 back in 1980. You could say this latest "egg-cellent" view has the Cassini science team licking their chops at the thought of future Prometheus images.

This raw, unprocessed image of Prometheus [pro-MEE-thee-us] , taken in visible light, was obtained by Cassini's narrow-angle camera at a distance of approximately 36,000 kilometers (23,000 miles).

The Cassini Equinox Mission is a joint United States and European endeavor. The Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the mission for NASA's Science Mission Directorate, Washington, D.C. The Cassini orbiter was designed, developed and assembled at JPL. For more information about the Cassini Equinox Mission visit: http://www.nasa.gov/cassini and http://saturn.jpl.nasa.gov.

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Envisioning Future Flight

Posted on January 29, 2010 by Danzig

Edric San Miguel's design concept, The Silent Airliner, was the first-place winner in the U.S

Today's students will be designing tomorrow's aircraft, and NASA's Fundamental Aeronautics Student Competition gives them a head start.

Each year, the competition challenges students to research a particular real-world issue in aeronautics and to develop their own solutions to the problem.

Past participants in NASA's Fundamental Aeronautics Student Competition said the experience was a rewarding one that helped them learn more about aeronautics and encouraged them to improve their approaches to research and creative problem-solving.

In the 2008-2009 competition, students were challenged to develop ideas for making commercial supersonic air transportation available by 2020. Contest participants did so by examining obstacles to supersonic transportation and proposing solutions. In an additional challenge, some students submitted designs for a small supersonic airliner.

The top U.S. individual winner won a $1,000 cash prize, and members of the top U.S. team split $1,500. International students were not eligible for cash prizes but received an engraved trophy. All participants received a NASA certificate and free student versions of two engineering software programs.

Edric San Miguel was the first-place winner in the U.S. individual category for his design concept, "The Silent Airliner." When he entered, San Miguel was a junior at the Norfolk Technical Center in Norfolk, Va.

San Miguel is a student in Norfolk Public Schools' NORSTAR Gifted Program, which promotes scientific research, robotics, inventions and innovations. He first entered the program after being told about it by his teacher, Joy Young, during his sophomore year.

"That year, I entered the competition as an individual and placed second in the U.S. individual awards category," he said. "I tied with a senior from Arizona. Last year, I decided that I would take on the next challenge of the contest as a high school junior. That is when I placed first place in the entire high school division."

The aeronautics contest is just one way San Miguel has been involved with NASA. During the summer, he participated in the NASA Langley Aerospace Research Summer Scholars project. "Through this program, I worked as an intern at NASA Langley's Systems Analysis and Concepts Directorate and Aeronautics Systems Analysis Branch," he said. He continued working as an intern through the fall session as a part-time intern. He plans to participate in the aeronautics contest again.

"The biggest thing I got out of this contest is the internship," he said. "Through this internship, I was able to work with NASA engineers and experience what aeronautical engineers do. I was able to make new friends with my fellow interns, establish contacts with engineers, and enter the pipeline into working for NASA."

San Miguel hopes to attend Virginia Tech and major in aerospace engineering and minor in business management.

Second place in the individual category went to Andrew Andraka, who was a sophomore at Bishop Hendricken High School in Warwick, R.I., at the time he designed his entry, "Next-Generation Supersonic Airliner."

"I learned about this contest two years ago when my dad pointed it out, noting it was a topic where I could write all I wanted about airplanes," he said. "The first essay I wrote was 'The Next Generation DC-3,' where I designed a hybrid aircraft encompassing a canard wing setup, coupled with a Custer Channel wing. I received an honorable mention for my essay, so I decided I would try again with the 'Next Generation Supersonic Airliner.'"

Participating in the contest, Andraka said, was both a good learning experience and an enjoyable opportunity. "I learned a lot more about airline design and the thought process entailed to devise original concepts," he said. "It also gave me a good excuse to expand my library of aviation resources."

Andraka said that after majoring in aerospace engineering, he hopes to start an aircraft research and manufacturing company, specializing in light-sport aircraft and general aviation aircraft. He is working on flight training and hopes to be a private pilot with multiple endorsements before graduating college.

Jason Jong and Ziang Xie, of Arcadia High School in Arcadia, Calif., won first place in the U.S. team category of the contest. Jong, a junior at the time of the entry, and Xie, then a senior, named their design concept "The Lazarus T1."

"I had never participated in the NASA aeronautics competition nor any other NASA related or funded opportunities before entering the aeronautics competition," Jong said. "I don't quite remember, but I believe I was simply clicking around on NASA's Web site and came across the 'student contests' section for high schoolers. From the list, I saw the aeronautics contest, described as an aircraft design contest. At the time, I was an incoming sophomore. From about seventh-grade, I have had a lot of enthusiasm with airplanes, reading books, and searching the Web, so naturally, the contest was something I really really gravitated towards. I made a goal to enter, but unfortunately I waited until my junior year before I organized the completion of the project.

"The most rewarding aspect of entering this contest was the openness in creativity the contest allowed to designers," Jong said. "Though I have seen many plane designs through photos online, it was not until I entered this competition that I began piecing together feasible airplane designs of my own and developing my own imagination, like a precursor to actual aerospace engineering. It really brought a sense of creativity that I find rewarding, considering what we were able to accomplish."

Jong is currently applying to colleges. "My intended major is physics, which I have always liked," he said. "However, engineering seems a likely major for me as well, as my dad is a civil engineer. I'm keeping my options open for now. And, if I don't get into college, the Air Force sounds like a mighty fun place to go too!"

Xie heard about the contest through Jong. "I had never participated in this or any other NASA-affiliated contest before, with the exception of a regional Science Bowl competition at JPL (NASA's Jet Propulsion Laboratory), and at first I was hesitant about entering with my minimal knowledge," he said. "I gradually became more interested in the contest, however, as my teammate described how our submission would address issues with supersonic flight. We decided Jason would handle most of the basic design components, and I would work on creating a CAD model of our plane as well as help research technological advances, which might make supersonic flight more plausible in the future.

"The Fundamental Aeronautics competition piqued my interest in aeronautics and also helped me learn how to collaborate with a teammate in writing a design proposal," Xie said. "Most importantly, I learned how to quickly research and become more knowledgeable about a specific field."

Xie is currently attending UC Berkeley, majoring in electrical engineering and computer science.

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NASA Provides Inside Look at International Space Station with Streaming Video

Posted on January 29, 2010 by Danzig

NASA soon will provide Internet viewers an inside look at astronauts working in space by streaming video live from the International Space Station's laboratories. The internal views are set to begin Feb. 1 and will be available during all crew duty hours.

Since March 2009, NASA has provided streaming video online of Earth and the station's exterior as the laboratory complex orbits 220 miles above Earth at 17,500 miles per hour. The new in-cabin streaming video includes audio of communications between Mission Control and the astronauts, when available.

Television from the station is available only when the complex is in contact with the ground through its high-speed communications antenna and NASA's Tracking and Data Relay Satellite System. During "loss of signal" periods, Internet viewers may see a test pattern. When the space shuttle is docked to the station, the stream will include video and audio of those activities.

The station is a unique partnership between the space agencies of the United States, Canada, Europe, Japan and Russia. Construction began in 1998 and will be completed in 2010. Twenty-two crews have lived aboard the orbiting laboratory since 2000, including the current crew of five. Station residents have conducted important scientific experiments and gathered data to help assist future missions.

To view the streaming station video on Feb. 1, visit:

http://www.nasa.gov/station

To find out when the station will be visible over your city, visit:

http://www.jsc.nasa.gov/sightings

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NASA Sets Shuttle Endeavour Prelaunch Events and Countdown Details

Posted on January 29, 2010 by Danzig

News conferences, events and operating hours for the news center at NASA's Kennedy Space Center in Florida are set for the upcoming launch of space shuttle Endeavour.

The shuttle's STS-130 mission to the International Space Station is scheduled to lift off at 4:39 a.m. EST on Sunday, Feb. 7. STS-130 is the final scheduled shuttle night launch.

Detailed countdown milestones, news briefing times and participants, and hours of operation for Kennedy's news center and media credentialing office are available at:

http://www.nasa.gov/mission_pages/shuttle/news

A NASA blog will provide countdown updates beginning at 11:30 p.m. on Saturday, Feb. 6. Originating from Kennedy, the blog is the definitive Internet source for information leading up to launch. During the mission, visitors to NASA's shuttle Web site can read about the crew's progress and watch the mission's three spacewalks live. As Endeavour's flight concludes, the NASA blog will detail the spacecraft's return to Earth. For NASA's launch blog and continuous mission updates, visit:

http://www.nasa.gov/shuttle

The NASA News Twitter feed will be updated during the launch countdown, mission and landing. To follow, visit:

http://www.twitter.com/NASA

STS-130 astronaut Nicholas Patrick will be tweeting about his pre-launch preparations and providing updates to his Twitter account during the shuttle mission. Follow Patrick at:

http://www.twitter.com/Astro_Nicholas

For NASA TV streaming video, scheduling and downlink information, visit:

http://www.nasa.gov/ntv

Endeavour's flight begins the final year of shuttle operations. Five missions are planned in 2010, with the final flight targeted for launch in September.

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Famous people with cancer

Posted on January 29, 2010 by Danzig

Instances of cancer are on the rise, and have become more and more common and more highly publicized in recent times. Many people know or are aware of someone that either has or has had cancer, whether this is a friend, relative or someone at work. There are many cases, of course, of famous people that have – or have had – cancer. Kate Jackson, perhaps the most famous of the original Charlie’s Angels from the original 1970s TV series, battled against cancer in 1987 and 1989, as did the singer and star of Grease, Olivia Newton John, who having been diagnosed in 1992 underwent surgery for a mastectomy and breast reconstruction.

Also of original Charlie’s Angels fame Jacelyn Smith found a lump back in 2002 and underwent treatment, including radiation and a lumpectomy. Many people, especially as the myth is precipitated by the mass media, believe that breast cancer only affects women. However Richard Roundtree, star of the original 1970s Blaxploitation classic Shaft, was also diagnosed with breast cancer in 1993 and underwent grueling rounds of chemotherapy and also a mastectomy.

Interestingly, not everyone opts for conventional forms of treatment when they are diagnosed with cancer, however scary a diagnosis it may be. Radical approaches to cancer treatment can cause considerable controversy when your are a celebrity – and such was the case for soap actress and author Suzanne Somers who opted to forgo standard cancer treatments in favor of holistic medicine and alternative therapies. Many believed at the time that this set a bad and even dangerous example to other sufferers and potential sufferers,

The singer-songwriter and former music teacher Sheryl Crow was also diagnosed with breast cancer in February 2006, and the condition was found to be at an early stage. She started off having only slightly invasive surgical treatment, followed-up with radiotherapy. In the following year, she made a documentary called Crazy Sexy Cancer. Her one-time husband, seven-time tour de France winner Lance Armstrong also suffered from testicular cancer and underwent chronic radiation therapy and surgery – and this was even before he won the tour!

Australian pop star and one-time Neighbors star, Kylie Minogue, also found herself facing a diagnosis of early-stage breast cancer in 2005. This caused her to put a halt to her grueling tour itinerary so that she could under chemotherapy and radiotherapy treatments. Showing just how much of an influence celebrities have on the general public consciousness with such things, her diagnosis caused a steep rise in women aged between 25-44 deciding to have breast imaging and biopsies to check for the disease.

Sex and the City’s Cynthia Nixon, who portrays the lawyer Miranda Hobbs in the highly successful show, underwent her battle with cancer in 2002 and initially stayed silent about her condition, choosing to campaign out of the media spotlight. She later became a cancer activist, and in 2008 became the ambassador and spokesperson for Susan G. Komen for the Cure.

Engineering Parallels Between Ephemerisle & Seasteading

Posted on January 29, 2010 by Danzig

There are a wide variety of opinions in the seasteading community about whether Ephemerisle is a plausible path to full seasteading. Here's my pre-event pitch of why Ephemerisle is useful. Post-event, I have an additional thought.

Our Ephemerisle structure and setup basically worked as plan, with a few exceptions. One is that it took longer than we expected, and was not completed by the noon Friday starting time (although everything did come together for Saturday evening).

Will Chamberlain – Thinking Structurally About Government

Posted on January 29, 2010 by Danzig

Will Chamberlain's talk at the second annual Seasteading Conference, "Thinking Structurally About Government", is now available online:

Henna Ceremony

Posted on January 29, 2010 by Danzig

The henna ceremony took place on the Saturday afternoon prior to the main party. It was an all women affair apart from myself my brother and uncle....

Nike Shox important part for everyone

Posted on January 29, 2010 by Danzig

If you want to make impression on your beloved ones or friends then it is very important to pay emphasis on clothes as well as on shoes you are going to wear. It is often seen that most of the people consider clothing as the important tool in enhancing their looks and ignore the other important accessories like shoes. But are they right in their opinionThe answer to above question is no Surely

Put the car on cruise control…

Posted on January 29, 2010 by Danzig

Well if only we could put our truck on cruise control and sit back and relax because it wouldn't have any problem finding where we are going since it's one of our regular spots...We decided that we might as well head back up the coast and try and get a bit of surfing and relaxing in so we left Shellharbour on Saturday and headed up towards one of our regular haunts Crescent Head. We just happen

The preparations required for time spent relaxing are rigorous

Posted on January 29, 2010 by Danzig

Not really. We're leaving for Hawaii on Sunday and have probably spent a half an hour planning our trip. No worries hang loose The local park ranger on Kauai has informed me that 'Kauai loves you' I'm pretty excited about this. This is the bookmarked 'I need some sun badly' vacation for most AKers. With the credit card companion fares it's way cheaper for us to fly to HI than it is to

Day 9

Posted on January 29, 2010 by Danzig

So my first day in Auckland. It's lovely weather here. It's still really hot and I feel like I'm tanning by the second. However it's a lot cooler and there's a lot more breeze than Australia. This is my idea of perfect weather. Blue skies too which are my favourite... The reason that I will tan so fast is because of the massive great hole in the ozone layer. I was having a discussion with an Aus

The material of tiffany

Posted on January 29, 2010 by Danzig

If you like the exclusive sculpt of wedding rings FUSION cycle of the use of elegant position sophisticated nested procedure of lawwith a broad extent of mix and bout scuff means carry to meet the diverse wishes of consumers at various levels among Keyi special preferences signetresonate goods can also add semblance every year representing year durable emotions. If you want in the wedding de

tips of replacing a laptop hard drive

Posted on January 29, 2010 by Danzig

A year ago I bought a dell e1505 notebook cheaply.but I have replaced almost all of the laptops accessories during the year.now I must replace the hard drivebut how do I replaceDonrsquot rush into replacing the hard drive before troubleshooting the problem. The first step I take when working on any laptop or notebook computer is to remove the battery. Even if the power button is well prote

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