Drugmakers Are Desperate to Know Why Placebos Are Getting More Effective

Fascinating article from Wired: Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today’s economy, the fate of a long-established company can hang on the outcome of a handful of tests.
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Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary. By the late ’90s, for example, the classic antianxiety drug diazepam (also known as Valium) was still beating placebo in France and Belgium. But when the drug was tested in the US, it was likely to fail. Conversely, Prozac performed better in America than it did in western Europe and South Africa. It was an unsettling prospect: FDA approval could hinge on where the company chose to conduct a trial.
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In one study, Benedetti found that Alzheimer’s patients with impaired cognitive function get less pain relief from analgesic drugs than normal volunteers do. Using advanced methods of EEG analysis, he discovered that the connections between the patients’ prefrontal lobes and their opioid systems had been damaged. Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer’s patients don’t get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.

Benedetti often uses the phrase “placebo response” instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body’s “endogenous health care system.” Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumors. It also works in reverse to produce the placebo’s evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
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Moreover, a pill’s shape, size, branding, and price all influence its effects on the body. Soothing blue capsules make more effective tranquilizers than angry red ones, except among Italian men, for whom the color blue is associated with their national soccer team—Forza Azzurri!

Medical research presents significant difficulties. The funding of the health care system also distorts behavior and pushes companies to focus on being able to justify selling drugs instead of focusing on finding effective solutions. Even without incentives distorting behavior, the challenges are difficult enough. Adding the distortions just makes it worse.

It is wonderful we have so many scientists accepting these challenges and spending their careers fighting the odds to help find us wonderful health breakthroughs.

Loon – Balloon Enabled Internet

Project Loon, from Google:

The Internet is one of the most transformative technologies of our lifetimes. But for 2 out of every 3 people on earth, a fast, affordable Internet connection is still out of reach.
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We believe that it might actually be possible to build a ring of balloons, flying around the globe on the stratospheric winds, that provides Internet access to the earth below. It’s very early days, but we’ve built a system that uses balloons, carried by the wind at altitudes twice as high as commercial planes, to beam Internet access to the ground at speeds similar to today’s 3G networks or faster. As a result, we hope balloons could become an option for connecting rural, remote, and underserved areas, and for helping with communications after natural disasters.

Google testing out this system now in New Zealand. If they can get it to work they plan to use ballons to provide wireless internet access to hundreds of millions, or even billions, of people that don’t have access now. These ballons would float about 20 km above earth in the stratosphere (so well above where commercial airline traffic) and they are really working somewhat like to satellites.

Though ballons are much cheaper to put in place than satellites they also offer significant problems as they get blow around by wind (which is why they haven’t been used before and why Google is going to experiment to see if they can get it to work). The ballons will use solar power and be controlled by a mission control to move into different wind zones to position themselves.

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Introduction to Fractional Factorial Designed Experiments

Scientific inquiry is aided by sensible application of statistical tools. I grew up around the best minds in applied statistics. My father was an eminent applied statistican, and George Box (the person in the video) was often around our house (or we were at his). Together they wrote Statistics for Experimenters (along with Stu Hunter, not related to me) the bible for design of experiments (George holds up the 1st edition in the video).

The video may be a bit confusing without at least a basic idea of factorial designed experiments. These introductory videos, by Stu Hunter, on Using Design of Experiments to Improve Results may help get you up to speed.

This video looks at using fractional factorials to reduce the number of experiments needed when doing a multifactor experiment. I grew up understanding that the best way to experiment is by varying multiple factors at the same time. You learn much quicker than One Factor At a Time (OFAT), and you learn about interactions (which are mainly lost in OFAT). I am amazed to still hear scientists and engineers talk about OFAT as a sensible method or even as the required method, but I know many do think that way.

To capture the interactions a full factorial requires an ever larger number of experimental runs to be complete. Assessing 4 factors requires 16 runs, 6 would require 64 and 8 would require 256. This can be expensive and time consuming. Obviously one method is to reduce the number of factors to experiment with. That is done (by having those knowledgable about the process include only those factors worth the effort), but if you still have, for example, 8 very important factors using a fractional factorial design can be very helpful.

And as George Box says “What you will often find is that there will be redundant factors… and don’t forget about those redundant factors. Knowing that something doesn’t matter is almost as important as knowing what does.” If you learn a factor isn’t having an affect you may be able to save money. And you can eliminate varying that factor in future experiments.

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Appropriate Technology Health Care Solution Could Save 72,000 Lives a Year

We need more medical solutions that serve the majority of humanity instead of just the rich. Some medical research is innately costly and therefore require large costs to pay back the investment. But too little concern is shown for solutions that help people (with so much focus only on solutions that will make organizations rich).

Cheap vinegar test cut cervical cancer deaths in India; could help many poor countries

This low-tech visual exam cut the cervical cancer death rate by 31 percent, the study found. It could prevent 22,000 deaths in India and 72,600 worldwide each year, researchers estimate.
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More progress against cervical cancer may come from last month’s announcement that two companies will drastically lower prices on HPV vaccines for poor countries. Pilot projects will begin in Asia and Africa; the campaign aims to vaccinate more than 30 million girls in more than 40 countries by 2020.

India continues to invest in medical research for solutions that are affordable to a majority of the world. The rich health care companies largely neglect the majority to focus on the most wealthy.

Rubber Trees

I think rubber trees are pretty cool, dripping out nice latex is just neat.

Photo of rubber trees in Khao Lak, Thailand

Latex is collected from trees which is then treated to make rubber. Hevea brasiliensis (originally found the Amazon basin in Brazil), the ParÃ¡ rubber tree, sharinga tree, or, most commonly, the rubber tree, is a tree belonging to the family Euphorbiaceae. Gutta-percha (Palaquium) is a genus of tropical trees native to Southeast Asia. The milky latex extracted from the trees is the primary source of natural rubber. Now refining petroleum is an alternative way for creating products that required rubber previously, but rubber is still economically important.

In 1876, Henry Wickham gathered thousands of para rubber tree seeds from Brazil, and these were germinated in Kew Gardens, England. The seedlings were then sent to India, Ceylon (Sri Lanka), Indonesia, Singapore and British Malaya (now Malaysia). Malaya was later to become the biggest producer of rubber. In the early 1900s, the Congo, Liberia and Nigeria also became significant producers of natural rubber latex.

Rubber tree seed from near Fraser’s Hill, Malaysia, by John Hunter.

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Webcast: Examining the Scientific Basis Around Exercise and Diet Claims

Tim Noakes is the Director of UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Science, University of Cape Town and Professor, Discovery Health Chair of Exercise and Sports Science, University of Cape Town.

Tim examines some questions on science and exercise and health in the webcast. He shows the problem with drinking too much during exercise and the correlation of hospital admissions correlated to the sport drinks marketing and changing of the official drinking guidelines. He also discusses the outdated ideas related to lactic acid and muscles.

He is currently studying the science of food and human health and is skeptical of low fat health claims: “No evidence that dietary fat is related to heath disease.” He is certainly more knowledgable than I but I would still be cautious of completely accepting that premise. It does seem to me there is lots of evidence that claims of causation between eating a high fat diet and heart disease were too strong (many other factors were critical – such as weight, exercise, genetics, unsaturated fat v. saturated fat…).

Tim Noaks: “50% of what we teach is wrong; the problem is we don’t know which 50% it is. Our job as educated people is to spend our lifetime trying to figure out which 50% is which. Until it is disproven accept that for which the evidence appears solid and logical and is free of covert or overt conflicts of interest, because unfortunately industry is driving what you believe in many many things. But don’t ever dismis lightly that for which there is credible evidence… and there is such clear evidence the diets we are eating are horrendous.”

As I have said before, scientific literacy is critical to allow us to make those judgements about what is credible evidence and what are outright lies, foolish claims or highly suspicious claims tainted by conflicts of interest.

Clay Water Filters for Ghana

Pure Home Water, Ghana manufactures and distributes AfriClay Filters in an effort to bring clean water to 1 million people. So far they have delivered filters to provide 100,000 people clean water.

The process is simple. Water is placed in a clay filter and gravity pulls the water through the pores left in the clay during firing.

Sediment and bacteria are filtered out in several ways:

Physical straining: the particles are too large to fit through the pores in the clay
Sedimentation or adsorption: particles come to rest on or stick to the clay
Inertia: friction in the pores keeps the particles from passing through

Bacteria are also killed by a coating of colloidal silver (a disinfectant), which we apply to all filters that pass our quality control tests. While sediment and bacteria are filtered out, the molecules of water are small enough to pass through the pores in the clay.

The filters are sold to those who will use them. The effort has shown a willingness to pay by villagers in remote Northern Ghana (those earning < US$1/day). I imagine (I am just guessing) the prices are subsidized; in the last decade more (most?) appropriate technology solutions will have those benefiting pay something for the benefits they receive. My nephews are working on a similar effort in India, using bio sand filters, I plan to post more on that later. There is current a campaign to help fund the delivery of water filters to Indian villages.

Europe Bans Certain Pesticides, USA Just Keeps Looking, Bees Keep Dying

For years the bee colony collapse disorder has been showing the difficulty of the scientific inquiry process. And that difficulty often becomes more difficult if interests with lots of money at stake want to block certain conclusions.

One-Third of U.S. Honeybee Colonies Died Last Winter, Threatening Food Supply

Multiple factors — pesticides, fungicides, parasites, viruses and malnutrition — are believed to cause the losses, which were officially announced today by a consortium of academic researchers, beekeepers and Department of Agriculture scientists.

“We’re getting closer and closer to the point where we don’t have enough bees in this country to meet pollination demands,” said entomologist Dennis vanEngelstorp of the University of Maryland, who led the survey documenting the declines.

Beekeepers lost 31 percent of their colonies in late 2012 and early 2013, roughly double what’s considered acceptable attrition through natural causes. The losses are in keeping with rates documented since 2006, when beekeeper concerns prompted the first nationwide survey of honeybee health. Hopes raised by drop in rates of loss to 22 percent in 2011-2012 were wiped out by the new numbers.
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Most losses reported in the latest survey, however, don’t actually fit the CCD profile. And though CCD is largely undocumented in western Europe, honeybee losses there have also been dramatic. In fact, CCD seems to be declining, even as total losses mount. The honeybees are simply dying.

“Even if CCD went away, we’d still have tremendous losses,” said entomologist Diana Cox-Foster at Pennsylvania State University. “CCD losses are like the straw that breaks the camel’s back. The system has many other issues.”

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Given Tablets but No Teachers, Kids Teach Themselves – Having Never Seen Advanced Technology Before

In a repetition of an experiment I have posted about here on the Curious Cat Science and Engineering Blog before (Letting Children Learn – Hole in the Wall Computers): Given Tablets but No Teachers, Ethiopian Children Teach Themselves

The experiment is being done in two isolated rural villages with about 20 first-grade-aged children each, about 50 miles from Addis Ababa. One village is called Wonchi, on the rim of a volcanic crater at 11,000 feet; the other is called Wolonchete, in the Great Rift Valley. Children there had never previously seen printed materials, road signs, or even packaging that had words on them, Negroponte said.

Earlier this year, OLPC workers dropped off closed boxes containing the tablets, taped shut, with no instruction. “I thought the kids would play with the boxes. Within four minutes, one kid not only opened the box, found the on-off switch … powered it up. Within five days, they were using 47 apps per child, per day. Within two weeks, they were singing ABC songs in the village, and within five months, they had hacked Android,” Negroponte said. “Some idiot in our organization or in the Media Lab had disabled the camera, and they figured out the camera, and had hacked Android.”

Nicholas Negroponte has tendency to overstate the fact from what I remember. I don’t think what he claims as “hacking Android” here is what a real scientist would claim as than is a write up of the results of the experiment. He could well mean they updated a setting or some similar thing. It is a shame to mislead when the bare facts are so cool. And possibly he isn’t misleading – I just am worried he is.

Also what does 47 apps per day mean? I can’t understand how you can usefully (including entertainment do that in any sensible way) – I doubt I use 15 applications in a month and I use the computer hours every single day. Makes me worry that “using” is not a very enlightening piece of data – instead just trying to make it seem like using 47 must mean they are engaged; it seems more likely to me to mean they are not used successfully so they have to go try something else or they are counting “used” in ways we wouldn’t.

Once a week, a technician visits the villages and swaps out memory cards so that researchers can study how the machines were actually used.

These kinds of experiments are very cool. They show how intrinsically curious we are are. Sadly our schools often beat the curiosity out of kids instead of engaging it.

The Wonderful Coconut

One of the treats of living in a tropical climate is drinking coconut water. I love drinking the water from fresh coconuts. This video provides insight into the many uses of all parts of the coconut tree.

The Truth About Coconut Water by Kathleen M. Zelman, MPH, RD, LD – WebMD

[coconut water] has fewer calories, less sodium, and more potassium than a sports drink. Ounce per ounce, most unflavored coconut water contains 5.45 calories, 1.3 grams sugar, 61 milligrams (mg) of potassium, and 5.45 mg of sodium compared to Gatorade, which has 6.25 calories, 1.75 grams of sugar, 3.75 mg of potassium, and 13.75 mg of sodium.
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There are some health benefits to consuming coconut water. It’s an all-natural way to hydrate, reduce sodium, and add potassium to diets. Most Americans don’t get enough potassium in their diets because they don’t eat enough fruits, vegetables, or dairy, so coconut water can help fill in the nutritional gaps.

Beyond that, the scientific literature does not support the hype that it will help with a laundry list of diseases. “There is a lot of hype about coconut water, yet the research is just not there to support many of the claims and much more research is needed,” says Cheung.

I have tried bottled coconut water which was pitiful. I don’t know if that was just a bad type and good options exist or the fresh stuff is just much much better. But I’ll stick to fresh coconut water as long as I can.