Reflections of a Doctor Who Experienced an Acute Medical Event:
The Acute vs. Chronic Conundrum

 

 

By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.

 

 

The Journals and airways are filled with discussions of Patient Centered Care. Executive agencies and regulators have been charged with pursuing research defining, evaluating and implementing patient centered approaches to healthcare interventions. Despite the focus on limiting spending for actual care, significant resources have been allocated to the Agency for Healthcare Research and Quality (AHRQ) and the Patient Centered Outcomes Research Institute (PCORI) to develop new initiatives exploring the potential for comparative effectiveness research to help patients make informed choices and craft mechanisms to present and disseminate the data in formats facilitating access by patients.

 

Unhappily, I recently needed to access the health care system with an emergent, serious, and complex problem. After two weeks of exchanging cold viruses with my wife, who is also a physician, I suddenly noticed that both my hands and feet were numb. Within 24 hours I had modest leg weakness, and after another day was unable to walk unassisted, fasten buttons, tie shoes, or write. I diagnosed the problem pretty quickly, and by the time I called my doctor was confident that I had Guillain-Barre syndrome and would need admission. We met in the emergency room, and I spent four surreal days in the hospital receiving Intravenous immunoglobulin (IVIG) treatment and careful monitoring.

 

Once all were confident that the weakness had peaked and ventilator support would be unnecessary, I was discharged to outpatient occupational and physical therapy and an uncertain future where the potential for prolonged disability and discomfort, while unpredictable, loom large.

 

Thinking about this still evolving experience (and since I remain in the midst of it, there will be additional thoughts) one immediate insight is that we need to separate acute and emergent from longer term chronic care related decisions when considering what information patients need, how it should be communicated, and how patients can reasonably be expected to engage productively. During the acute stage I was too anxious, and impaired, to be a significant partner in my care. I needed smart, knowledgeable physicians that I trusted to act in my best interest. As the situation progresses to a more chronic phase, I shall be a much more effective participant in determining rehabilitation regimens and the rate of return to normal activities.

 

Both our rhetoric and our research need to acknowledge, and explicitly address the reality that the decision to stent a coronary artery or implant an intra-ventricular defibrillator in the setting of a myocardial infarction is fundamentally different from the decision to ?watchfully wait’ or initiate treatment in prostate cancer or the decision to have (or not) a screening mammogram in one’s 40’s. Some decisions, due to their acuity and complexity, are less amenable to collaborative decision making than others. Research focusing on how these different types of decisions are defined and framed for differently abled and motivated patients, as well as how data are presented and how medical professionals can best help patients address these very different types of challenges, ought to be key elements of efforts to enable patient centered care.

 

More to follow in the future…………

How We’re Creating “Terminator Vision” in Your Future Contact Lenses

 

 

 Terminator Vision

 

Babak Parviz, electrical engineer at theUniversityofWashington, as told to Flora Lichtman (PopSci.com, March 02, 2012):

 

 

 

We made a lens that displays a single pixel that can be turned on and off wirelessly. An integrated circuit stores the energy, and a light-emitting diode shoots 1) ___ toward the eye, but the optics are tricky. You can’t focus on something that’s that close. To correct this, we put a series of tiny lenses between the LED and the eye-imagine holding your finger too close to your eye so it’s blurry; you could bring it into focus by putting a magnifying 2) ___ between your eye and your finger.

 

So far, our display has only one pixel. But someday you could use the lenses to consolidate all the displays you interact with on a daily basis – your clock, computer, television and phone – into one personal display in your 3) ___. In the distant future, your contact lenses could augment your reality. If you were in a bare hallway, the 4) ___ in your contact could put paintings on the wall.

 

The light-emitting part of the contact lens is opaque, but these little dark spots shouldn’t obscure vision. The control circuitry and the radio, harvest energy from a transmitter at the edge of the lens and communicate with the world. They don’t block the view either. We don’t have permission to test the lenses on humans yet, but 5) ___ have worn it, and the lens was safe and functional.“

 

In CCNY physics professor Michio Kakus new book Physics of the Future, he predicts that these futuristic contact lenses will be the basis of all future media. cell phones and televisions will be replaced by these contact lenses and we’ll all have a pair. Imagine being able to access the Internet through the contact lenses on your eyeballs. Blink, and you’d be online. Meet someone, and you’d have the ability to immediately search their 6) ___. And if your friend happens to be speaking a different language, an instantaneous translation could appear directly in front of you. That might sound farfetched, but it’s something that might very well exist in 30 years or less, says theoretical physicist Dr. Kaku. “The first people to buy these contact lenses will be college 7) ___ studying for final exams,“ he explains, “they’ll see the exam answers right in their contact lenses. In a cocktail party, you will know exactly who to suck up to, because you’ll have a complete read out of who they are…. These already exist in some form [in the military]. You place [a lens] on your helmet, you flip it down, and immediately you see the Internet of the battlefield? all of it, right on your 8) ___.“

 

Kaku also explains how, in the future, our brains might be able to interface with artificial intelligence. He describes one study in which computer 9) ___ were placed into the brains of paralyzed stroke patients atBrownUniversity. The patients learned that by thinking certain thoughts, they could manipulate a cursor on a computer screen. “It takes a while – it takes a few hours – but after a while, you realize that certain thoughts will move the cursor in certain directions,“ he says. “After a while ? [the patients] were able to read email, write email, surf the Internet, play video games, guide wheelchairs – anything you can do on a computer, they can do as well, except they’re trapped inside a paralyzed body.“

 

Similar technology could be used in the future to control robots that can go places where 10) ___ can’t, says Kaku. Some have said that if these contact lenses are going to be the things decorating our rooms and basically making up our world, why don’t we just plug ourselves into a computer, as seen in the film The Matrix?  Maybe we already are, and we just don’t know it yet?..that is, clearly, we’re all plugged into a global network, right now?..Joyce Hays, Target Health Inc.

 

ANSWERS:1) light; 2) glass; 3) eye; 4) computer; 5) animals; 6) identity; 7) students; 8) eyeball; 9) chips; 10) humans

 

Credit: Andrea Brizzi/Doubleday

 

Michio Kaku is an author and the Henry Semat Professor of Theoretical Physics at the City University of New York. His books include Hyperspace, Visions and Beyond Einstein

 

 

Another Glimpse into the Future with This 2012 Humanized Robot.


 

Biology, Evolution and Past Global Warming Affected Body Size of Mammals

This is an artist’s reconstruction of Sifrhippus sandrae (right) touching noses with a modern Morgan horse (left) that stands about 5 feet high at the shoulders and weighs about 1,000 pounds. Sifrhippus was the size of a small house cat (about 8.5 pounds) at the beginning of the Eocene (approximately 55.8 million years ago) and is the earliest known horse. (Credit: Danielle Byerley, Florida Museum of Natural History)

 

 

 

As scientists continue developing climate change projection models, paleontologists studying an extreme short-term global warming event have discovered direct evidence about how mammals respond to rising temperatures. In a study appearing in Science (2012; 335:959), researchers from eight institutions led by scientists from the University of Florida and University of Nebraska found a correlation between temperature and body size in mammals by following the evolution of the earliest horses about 56 million years ago: As temperatures increased, their body size decreased.

 

“Horses started out small, about the size of a small dog like a miniature schnauzer,“ said co-author Jonathan Bloch, associate curator of vertebrate paleontology at the Florida Museum of Natural History on the UF campus. “What’s surprising is that after they first appeared, they then became even smaller and then dramatically increased in size, and that exactly corresponds to the global warming event, followed by cooling. It had been known that mammals were small during that time and that it was warm, but we hadn’t understood that temperature specifically was driving the evolution of body size.“

 

Sifrhippus, the earliest-known horse, first appeared in the North American fossil record during the Paleocene-Eocene Thermal Maximum. During this 175,000-year climate event, increased concentrations of carbon dioxide in the atmosphere and oceans caused average global temperatures to rise 10 to 20 degrees. By analyzing the size and isotopes of fossils collected inWyoming’sBighornBasin, researchers traced the evolution of Sifrhippus from an estimated 12-pound animal that shrank during a 130,000-year period about 30% to 8.5 pounds – the size of a small house cat – then increased to about 15 pounds during the next 45,000 years.

 

“This is the highest-resolution terrestrial record of its kind from anywhere in the world and it shows how climate changed in Wyoming at that time,“ said lead author Ross Secord, who began geochemical analysis of the horse teeth and other mammals as a postdoctoral researcher with Bloch before joining the University of Nebraska-Lincoln in 2008. “When Jon and I started plotting oxygen data from the mass spectrometer, we could immediately see that the shifts in size of horses and temperature were mirror images of each other.“ Bloch said the project began about seven years ago when former UF student and study co-author Stephen Chester, now an anthropology doctoral candidate atYaleUniversity, measured horse teeth that seemed to be too large for their age and became smaller through the geologic section. The findings raise important questions about how animals might respond to future rapid climate change.

 

“We’re seeing about a third of the mammals getting smaller and some of them getting a lot smaller, by as much as half of their original body size,“ Secord said. “Because warming happened much slower during the Paleocene-Eocene Thermal Maximum, mammals had more time to adjust their body size. So, it’s not clear that we’re going to see the same thing happening in the near future, but we might.“ Philip Gingerich, who first recorded the phenomenon of decreasing body size during the Paleocene-Eocene Thermal Maximum in 1989, said the study documentation clearly demonstrates the relationship between temperature and body size. He agrees this may occur as a result of current warming patterns. “I joke about this all the time – we’re going to be walking around 3 feet tall if we keep going the way we’re going,“ said Gingerich, a researcher at the University of Michigan and director of its Museum of Paleontology. “Maybe that’s not all bad and if that’s the worst it gets, it will be fine. You can either adapt, or you go extinct, or you can move, and there’s not a lot of place to move anymore, so I think it’s a matter of adaptation and becoming smaller.“

 

Researchers also analyzed correlations with aridity and carbon dioxide levels but found temperature to be the most likely driving factor in body size. Although little is known about how animals arrived inNorth Americaat that time, the Paleocene-Eocene Thermal Maximum is a significant event in geologic time in terms of mammalian history, Bloch said. “The PETM is really important because it marks the beginning for the first appearance of several major groups of mammals, including crown-group primates (ancestors of modern primates) and the first even- and odd-toed modern ungulates (mammals with hooves),“ Bloch said. “This sets the scene for the entire diversity of animals we see on the planet today.” Source: ScienceDaily.com

Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury

 

 

Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery. As a result, a study published in the New England of Medicine (2012; 366:819-826), designed to evaluate the safety and efficacy of amantadine, enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models.

 

Results showed that during the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007). The treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. After the 4-week treatment period, the rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events.

 

According to the authors, amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness.

V. NEUROLOGY

Blockade of Learning and Memory Genes May Occur Early in Alzheimer’s Disease

 

Alzheimer’s disease (AD) is the most common cause of dementia in older adults, and affects as many as 5.1 million Americans. In the most common type of AD, symptoms usually appear after age 65. A hallmark of the disease is the accumulation of a toxic protein fragment called beta-amyloid in brain cells, which is widely believed to be the initial trigger for neurodegeneration.

 

According to an article published online in Nature (29 February 2012), repression of gene activity in the brain appears to be an early event affecting people with AD. The study found that a protein called histone deacetylase 2 (HDAC2) accumulates in the brain early in the course of AD in mouse models and in people with the disease. HDAC2 is known to tighten up spools of DNA, effectively locking down the genes within and reducing their activity, or expression. In the mice, the increase in HDAC2 appears to produce a blockade of genes involved in learning and memory. Preventing the build-up of HDAC2 protected the mice from memory loss.

 

The study examined two mouse models of AD around the time that the mice begin to show signs of brain cell degeneration. Results showed that the mice had higher levels of HDAC2, but not other related HDAC proteins, specifically in the parts of the brain involved in learning and memory. This increase in HDAC2 was associated with a decrease in the expression of neuronal genes that HDAC2 is known to regulate. Use of a gene therapy approach to reduce the levels of HDAC2 prevented the blockade of gene expression. The treatment also prevented learning and memory impairments in the mice. It did not prevent neuronal death, but it did enhance neuroplasticity — the ability of neurons to form new connections.

 

The study also examined HDAC2 levels in autopsied brain tissue from 19 people with AD at different stages of the disease, and from seven unaffected individuals. Even in its earliest stages, the disease was associated with higher HDAC2 levels in the learning and memory regions of the brain.

 

The authors theorized that HDAC2 is brought into play by beta-amyloid since it was found that exposing mouse neurons to beta-amyloid caused them to produce more HDAC2.

 

Vaccines and other therapies aimed at reducing beta-amyloid are in clinical trials. Efforts to reduce HDAC2 may provide a complementary approach to treating AD. The authors previously reported that HDAC inhibitor compounds can protect against signs of AD in mice. A problem with such compounds is that they inhibit not only HDAC2 but related HDAC proteins, leading to broad and potentially toxic effects. The new study supports the possibility of developing drugs more specifically targeted to HDAC2 and the pathology of AD. The authors are working to identify HDAC2-specific inhibitors that could be developed into drugs and moved into trials.

Poly-N-Acetyl Glucosamine in Patients with Venous Leg Ulcers

 

 

Standard care for venous leg ulcers (VLUs) has remained unchanged over several decades despite high rates of initial treatment failure and ulcer recurrence. As a result, a study published online in the Journal of theAmericanAcademyof Dermatology (27 May 2011), was performed to evaluate the efficacy, safety, and tolerability of an advanced, poly-N-acetyl glucosamine (pGlcNAc), nanofiber-derived, wound-healing technology among patients with VLUs.

 

The investigation was a randomized, investigator-blinded, parallel-group, controlled study. Eligible patients were randomized to treatment with standard care plus pGlcNAc (applied only once, every other week, or every 3 weeks) or to standard care alone. The primary end point was the proportion of patients with complete wound healing at week 20 in the intent-to-treat population (all randomized subjects), with last observation carried forward.

 

Results showed that among 82 randomized patients, 71 completed the study with 7 lost to follow-up and 4 discontinued because of systemic infection. There were no significant group differences with regard to baseline demographic, illness, and VLU characteristics.

 

At 20 weeks, the proportion of patients with completely healed VLUs was 45.0%, 65.0% and 86.4%, for groups receiving standard care plus pGlcNAc only once, every 3 weeks, every other week, respectively, versus 45.0%  for those receiving standard care alone (P <0.01 for treatment every other week vs. standard care).

 

According to the authors, this pilot study results suggest that the pGlcNAc advanced wound-healing technology is well tolerated and effective.

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FDA Approves Two New Pancreatic Enzyme Products to Aid Food Digestion

 

 

Adults with chronic pancreatitis, a continuing, chronic inflammatory process of the pancreas, or those who have had some or all of their pancreases removed (pancreatectomy) may not digest food normally because they lack needed enzymes or because their enzymes are not released into the bowel (intestine).

 

Two new pancreatic enzyme products used to help aid food digestion, Ultresa (pancrelipase) and Viokace (pancrelipase), have been approved by the FDA. Ultresa is a delayed-release capsule used to treat children and adults with cystic fibrosis, a serious genetic disorder affecting the lungs and other organs, or other conditions where patients cannot digest food normally because their pancreas does not make enough pancreatic enzymes. Viokace, in combination with a proton pump inhibitor, is used to treat adults who cannot digest food normally.

 

Ultresa and Viokace are the fourth and fifth pancreatic enzyme products approved by FDA. Other FDA-approved pancreatic enzyme products include Creon (2009), Zenpep (2009) and Pancreaze (2010). Approved pancreatic enzyme products meet FDA standards for safety, efficacy and product quality. Unapproved pancreatic enzyme products had been available for many years. FDA established a date of April 28, 2010 for the makers of pancreatic enzyme products to stop manufacturing and distributing unapproved products.

 

Ultresa and Viokace are marketed by Bridgewater, N.J.-based Aptalis Pharma U.S. Inc.

Target Health (www.targethealth.com) a full service e*CRO, is committed to serve the pharmaceutical community through knowledge, experience, technology and connectivity. Target Health strives to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. Target Health Inc. has fulltime staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. Target Health is committed to the paperless clinical trial and has developed a full suite of eClinical Trial software including:

 

 

1) Target e*CRF® (EDC Made Simple)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target e*Pharmacovigilance™

6) Target e*Monitoring™

7) Target Newsletter®

8) Target e*CTR™ (eSource, electronic medical record for clinical trials)

 

 

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