Category Archives: Health Care

Statistical Errors in Medical Studies

I have written about statistics, and various traps people often fall into when examining data before (Statistics Insights for Scientists and Engineers, Data Can’t Lie – But People Can be Fooled, Correlation is Not Causation, Simpson’s Paradox). And also have posted about reasons for systemic reasons for medical studies presenting misleading results (Why Most Published Research Findings Are False, How to Deal with False Research Findings, Medical Study Integrity (or Lack Thereof), Surprising New Diabetes Data). This post collects some discussion on the topic from several blogs and studies.

HIV Vaccines, p values, and Proof by David Rind

if vaccine were no better than placebo we would expect to see a difference as large or larger than the one seen in this trial only 4 in 100 times. This is distinctly different from saying that there is a 96% chance that this result is correct, which is how many people wrongly interpret such a p value.
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So, the modestly positive result found in the trial must be weighed against our prior belief that such a vaccine would fail. Had the vaccine been dramatically protective, giving us much stronger evidence of efficacy, our prior doubts would be more likely to give way in the face of high quality evidence of benefit.
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While the actual analysis the investigators decided to make primary would be completely appropriate had it been specified up front, it now suffers under the concern of showing marginal significance after three bites at the statistical apple; these three bites have to adversely affect our belief in the importance of that p value. And, it’s not so obvious why they would have reported this result rather than excluding those 7 patients from the per protocol analysis and making that the primary analysis; there might have been yet a fourth analysis that could have been reported had it shown that all important p value below 0.05.

How to Avoid Commonly Encountered Limitations of Published Clinical Trials by Sanjay Kaul, MD and and George A. Diamond, MD

Trials often employ composite end points that, although they enable assessment of nonfatal events and improve trial efficiency and statistical precision, entail a number of shortcomings that can potentially undermine the scientific validity of the conclusions drawn from these trials. Finally, clinical trials often employ extensive subgroup analysis. However, lack of attention to proper methods can lead to chance findings that might misinform research and result in suboptimal practice.

Why Most Published Research Findings Are False by John P. A. Ioannidis
Continue reading →

Norway Reduces Infections by Reducing Antibiotic Use

Norway conquers infections by cutting use of antibiotics

Twenty-five years ago, Norwegians were also losing their lives to this bacteria. But Norway’s public health system fought back with an aggressive program that made it the most infection-free country in the world. A key part of that program was cutting back severely on the use of antibiotics.

Now a spate of new studies from around the world prove that Norway’s model can be replicated with extraordinary success, and public health experts are saying these deaths — 19,000 in the U.S. each year alone, more than from AIDS — are unnecessary.

“It’s a very sad situation that in some places so many are dying from this, because we have shown here in Norway that Methicillin-resistant Staphylococcus aureus [MRSA] can be controlled, and with not too much effort,” said Jan Hendrik-Binder, Oslo’s MRSA medical advisor. “But you have to take it seriously, you have to give it attention and you must not give up.”

The World Health Organization says antibiotic resistance is one of the leading public health threats on the planet. A six-month investigation by The Associated Press found overuse and misuse of medicines has led to mutations in once curable diseases like tuberculosis and malaria, making them harder and in some cases impossible to treat.

Now, in Norway’s simple solution, there’s a glimmer of hope.

Antibiotics Breed Superbugs Faster Than Expected

We continue to endanger ourselves by using antibiotics inappropriately. This is one of many things that happen when the public at large is ignorant about science and ignores scientific evidence. I don’t believe people want to put other people’s lives in danger. But our behavior in the face of the evidence has us doing just that. I believe because we don’t value science rather than because we don’t care about putting others (and ourselves) in danger. Antibiotics Breed Superbugs Faster Than Expected

Bacteria don’t just develop resistance to one drug at a time, but to many — and at accelerated rates. That’s because antibiotics boost bacterial production of free-radical oxygen molecules that damage bacterial DNA. Repairs to the DNA cause widespread mutations, giving bacteria more chances to randomly acquire drug-resistant traits.
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Drug resistance is a serious public health concern. According to the federal Centers for Disease Control and Prevention, 70 percent of 1.7 million infections acquired in hospitals every year are resistant to at least one drug. Those infections annually kill 99,000 Americans — more than double the number that die in car crashes.

Drugs that once destroyed almost any bacteria now kill only a few, or don’t work at all. In the case of some drugs, like Cipro, the decline is dramatic: Where in 1999 it worked against 95 percent of E. coli, it treated only 60 percent by 2006. Against lung infection-causing Acinobacter, its effectiveness fell by 70 percent in just four years.

Though drug resistance is ultimately inevitable, conventional wisdom holds that antibiotics consumed at suboptimum doses hasten the process. Bugs that would have succumbed to a larger dose live to multiply, pushing the strain as a whole closer to resistance. That happens when a prescription goes unfinished, or when antibiotics used on farms enter food and water at low levels.
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Of the 35 million pounds of antibiotics consumed annually in the United States, 80 percent goes to farm animals. Much of it is used to treat diseases spread by industrial husbandry practices, or simply to accelerate growth. As a result, farms have become giant petri dishes for superbugs, especially multidrug-resistant Staphylococcus aureus, or MRSA, which kills 20,000 Americans every year – more than AIDS.

Alarming cases of farm-based MRSA and other diseases led to a proposed Congressional law restricting the use of agricultural antibiotics. That bill, supported by the American Medical Association and American Public Health Association, is opposed by farm lobbyists and remains stuck in committee.

Researchers Find Switch That Allows Cancer Cells to Spread

Researchers discovered of a specific protein called disabled-2 (Dab2) that switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body.

The process called epithelial-mesenchymal transdifferientiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of the solid tumor and transforming them into transient mesenchymal cell: cells with the ability to start to grow a new tumor.

This is often the fatal process in breast, ovarian, pancreatic and colon-rectal cancers.

Searching to understand how the EMT process begins, Ge Jin, who has joint appointments at the Case Western Reserve University School of Dental Medicine and the Lerner Research Institute at the Cleveland Clinic, began by working backwards from EMT to find its trigger. The researchers found that a compound called transforming growth factor-ÃŸ (TGF-ÃŸ) triggers the formation of the Dab2 protein. It was this protein, Dab2, that activated the EMT process.

He discovered that when the researchers knocked out Dab2, EMT was not triggered. “This is the major piece in cancer research that has been missing,” Jin said. Most tumors are epithelial in origin and have epithelial markers on their surface. The EMT process takes place when some of those cells dislodge from the surface and undergo a transformation into a fibrous mesenchymal cell maker with the ability to migrate.

“EMT is the most important step in this process,” said Jin. He was part of a six-member research team, led by Philip Howe from the Department of Cancer Biology at the Lerner Research Institute in a National Institute of Cancer-funded study. The research group studied the biological processes that initiated the cancer spread by using cancer cells in animal models.

“If we can understand the signaling pathway for modulating EMT, then we can design drugs to delay or halt EMT cells and control tumor progression,” Jin said. Beyond cancer, Jin said. “The process we discovered may lead to understanding how other diseases progress.”

Microbes Flourish In Healthy People

Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear? by Katherine Harmon

The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing?
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“Someone who didn’t have their microbes, they’d be naked,” says Martin Blaser, a professor of microbiology and chair of the Department of Medicine at New York University Langone Medical Center in New York City.
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Even though it is such an apparently integral and ancient aspect of human health, scientists are still grasping for better ways to study human microbiota—before it changes beyond historical recognition. Borrowing models from outside of medicine has helped many in the field gain a better understanding of this living world within us. “The important concept is about extinctions,” Blaser says. “It’s ecology.”
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The first step in understanding these systems is simply taking stock of what archaea, bacteria, fungi, protozoa and viruses are present in healthy individuals. This massive micro undertaking has been ongoing since 2007 through the National Institutes of Health’s (NIH) Human Microbiome Project. So far it has turned up some surprisingly rich data, including genetic sequencing for some 205 of the different genera that live on healthy human skin.

Despite the flood of new data, Foxman laughs when asked if there is any hope for a final report from the Human Microbiome Project any time soon. “This is the very, very beginning,” she says, comparing this project with the NIH’s Human Genome Project, which jump-started a barrage of new genetic research. “There are basic, basic questions that we don’t know the answers to,” she says, such as how different microbiota are between random individuals or family members; how much microbiota change over time; or how related the microbiota are to each other on or inside a person’s body.

Printing Bone, Muscle and More

A Pittsburgh-based research team has created and used an innovative ink-jet system to print “bio-ink” patterns that direct muscle-derived stem cells from adult mice to differentiate into both muscle cells and bone cells.

The custom-built ink-jet printer, developed at Carnegie Mellon’s Robotics Institute, can deposit and immobilize growth factors in virtually any design, pattern or concentration, laying down patterns on native extracellular matrix-coated slides (such as fibrin). These slides are then placed in culture dishes and topped with muscle-derived stem cells (MDSCs). Based on pattern, dose or factor printed by the ink-jet, the MDSCs can be directed to differentiate down various cell-fate differentiation pathways (e.g. bone- or muscle-like).

“This system provides an unprecedented means to engineer replacement tissues derived from muscle stem cells,” said Johnny Huard, professor of orthopedic surgery at the University of Pittsburgh School of Medicine and director of the Stem Cell Research Center at Children’s Hospital of UPMC. Huard has long-standing research findings that show how muscle-derived stem cells (MDSCs) from mice can repair muscle in a model for Duchenne Muscular Dystrophy, improve cardiac function following heart failure, and heal large bone and articular cartilage defects.

Weiss and Campbell, along with graduate student Eric Miller, previously demonstrated the use of ink-jet printing to pattern growth factor “bio-inks” to control cell fates. For their current research, they teamed with Phillippi, Huard and biologists of the Stem Cell Research Center at Children’s Hospital to gain experience in using growth factors to control differentiation in populations of MDSCs from mice.

The team envisions the ink-jet technology as potentially useful for engineering stem cell-based therapies for repairing defects where multiple tissues are involved, such as joints where bone, tendon, cartilage and muscle interface. Patients afflicted with conditions like osteoarthritis might benefit from these therapies, which incorporate the needs of multiple tissues and may improve post-treatment clinical outcomes.

The long-term promise of this new technology could be the tailoring of tissue-engineered regenerative therapies. In preparation for preclinical studies, the Pittsburgh researchers are combining the versatile ink-jet system with advanced real-time live cell image analysis developed at the Robotics Institute and Molecular Biosensor and Imaging Center to further understand how stem cells differentiate into bone, muscle and other cell types.

Disrupting Bacterial Communication to Thwart Them

Interrupting Bacterial Chatter to Thwart Infection

To measure their own numbers, bacteria produce, release, and detect chemical signals called autoinducers. As a population of bacteria grows, it releases more autoinducer into its environment. When individuals detect that a threshold level of autoinducer is present, they change their behavior – by releasing a toxin, for example.

Bassler and her colleagues disrupted these lines of communication by interfering with molecules called acyl-homoserine lactone (AHL) autoinducers, which drive quorum sensing among a kind of bacteria known as Gram-negative bacteria. Gram-negative bacteria include Pseudomonas, E. coli and Salmonella, and other disease-causing microbes. In the study, the team focused on Chromobacterium violaceum, which rarely infects human, but can be lethal to other organisms. C. violaceum lends itself to studies of quorum sensing because it produces a readily detected, bright purple dye when it detects that its population has reached a critical mass.
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The experiment shows that interfering with quorum sensing may provide an alternative to traditional antibiotics, Bassler says, and circumvent the problem of resistance that antibiotics foster by killing off susceptible bacteria but allowing resistant ones to survive and propagate.

Re-engineering the Food System for Better Health

Good food nation

According to the Centers for Disease Control, between 1980 and 2006 the percentage of obese teenagers in the United States grew from 5 to 18, while the percentage of pre-teens suffering from obesity increased from 7 to 17.
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Obesity is widespread due to our national-scale system of food production and distribution, which surrounds children – especially lower-income children – with high-calorie products…
90 percent of American food is processed – according to the United States Department of Agriculture – meaning it has been mixed with ingredients, often acting as preservatives, that can make food fattening.
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Now, in another report finished this October after meetings with food-industry leaders, the MIT and Columbia researchers propose a solution: America should increase its regional food consumption.
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Only 1 to 2 percent of all food consumed in the United States today is locally produced. But the MIT and Columbia team, which includes urban planners and architects, believes widespread adoption of some modest projects could change that, by increasing regional food production and distribution.

To help production, the group advocates widespread adoption of small-scale innovations such as “lawn to farm” conversions in urban and suburban areas, and the “10 x 10 project,” an effort to develop vegetable plots in schools and community centers. Lawns require more equipment, labor and fuel than industrial farming nationwide, yet produce no goods. But many vegetables, including lettuce, cucumbers and peppers, can be grown efficiently in small plots.
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As Albright sees it, the effort to produce healthier foods “fits right in with the health-care reform effort right now because chronic diseases are so costly for the nation.” America currently spends $14 billion annually treating childhood obesity, and $147 billion treating all forms of obesity.

Good stuff. We need to improve health in the USA. The current system is unhealthy and needs to be improved. The public good from improving the health of society is huge (both in terms of individual happiness and economic benefits).

Florence Nightingale: The passionate statistician

She brought about fundamental change in the British military medical system, preventing any such future calamities. To do it, she pioneered a brand-new method for bringing about social change: applied statistics.
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he statistics changed Nightingale’s understanding of the problems in Turkey. Lack of sanitation, she realized, had been the principal reason for most of the deaths, not inadequate food and supplies as she had previously thought.
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As impressive as her statistics were, Nightingale worried that Queen Victoria’s eyes would glaze over as she scanned the tables. So Nightingale devised clever ways of presenting the information in charts. Statistics had been presented using graphics only a few times previously, and perhaps never to persuade people of the need for social change.

Applied statistics is a tool available to all to achieve great improvement. Unfortunately it is still very underused. As George Box says: applied statistics is not about proving a theorem, it’s about being curious about things. The goal of design of experiments is to learn and refine your experiment based on the knowledge you gain and experiment again. It is a process of discovery.

Teenage Engineer’s Company Launches Safety Stair

Young engineer launches stair aid by Geoff Adams-Spink

A young woman from Sheffield has turned a GCSE coursework project into an award-winning stair-climbing device for older and disabled people. Ruth Amos has launched her StairSteady handrail at Naidex 2008 – the annual disability exhibition in Birmingham.

She told BBC News that she was inspired to create the device for the father of one of her teachers who had had a stroke. She won an award for her idea and has now set up a company to sell it. The StairSteady is a horizontal rail at 90 degrees to the wall or banister that people can hold on to as they go up or down stairs.
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The invention was then entered for the Young Engineer for Britain competition and won first prize.

Great stuff. Innovation doesn’t have to be amazing technology. Finding solutions that make people’s lives better is the key. And then showing some entrepreneurship is great, Ruth setup her company when she was 16. I wish her luck.