http://www.bio-medicine.org/medicine-news-1/Heart-Experts-Make-Boosting-Bystander-CPR-a-Priority-88449-1/

http://www.reuters.com/article/2012/01/09/us-vivus-idUSTRE8081LI20120109

http://online.wsj.com/article/BT-CO-20120110-706510.html

The passage below is from the MedMarket Diligence Report #S247, "Worldwide Wound Management, 2008-2017: Established and Emerging Products, Technologies and Markets in the U.S., Europe, Japan and Rest of World."

In the USA, medical devices fall within one of three categories depending on the complexity of the product and the invasiveness of its application. Fabric dressings are simple and minimally invasive, and to are designated as Class I devices, whereas products containing biomaterials of human or animal origin are in Class III. Some products that may be considered as examples of “Advanced Wound Care” (AWC, an abbreviation that is used widely in this report, and is synonymous with “advanced wound management”) are classified as Class II.

Medical devices require an investigational device exemption for clinical evaluation in humans; they are regulated through and receive 510(k) approval through a pre-market approval scheme regulated by the FDA in the USA, and are approved through the CE Marking process which was introduced in the early 1990s in Europe. 

Class I devices in Europe require development and manufacture to be performed under international standard quality control systems, and device dossiers to be managed by the manufacturing company. Class II devices require the dossiers to be submitted for review, and Class III devices require a more substantial device dossier to be compiled and submitted for review with more rigorous toxicological and clinical evaluation. In Europe, devices which incorporate biological materials derived from animals are classed automatically as Class III devices.

In the USA, pharmacological developments (with a pharmacologically active therapeutic benefit) automatically require an investigational new drug (IND) application. Biologic materials are reviewed for a biologics license application (BLA) through an IND by the CBER division of the FDA (CBER stands for Center for Biologic Evaluation and Research).

A wide range of regulatory approval conditions are applied to cell-based therapy products. Many of the technical challenges associated with creating a new tissue-engineered product are focused on the clinical proof phase, the regulatory requirements associated with making, proving effectiveness and safety of the product, and a number of controls on product claims and usage. Often the approach to achieving regulatory approval seems to be arduous, inconsistent and arbitrary. This is best illustrated by the complexity of approval for new tissue engineered products that exist today.

Autologous products for skin are currently available in the USA and new approaches to offering these cells wrapped up in customized services are becoming prevalent around the world. Allogeneic cell-based products for treatment of burn victims, skin conditions, and chronic wound care are now approved from a small number of suppliers in the USA, and several more on their way around the world.

Autologous tissue and cells transplanted during surgery do not have any regulatory requirements placed upon them by the US FDA. However, the devices used to carry out the surgical procedure are regulated as Class I medical devices. These products are required to be manufactured under Good Manufacturing Practices; they are regulated as Devices, and require 510(k)s in the USA. In Europe they are Class I medical devices.

Donated cadaveric tissue products produced to aid surgical construction must be manufactured under Good Manufacturing Practices (GMP) with ATSB or FDA approved manufacturing in the USA, and require Pre-Market Application (PMA) in the USA if extensively processed between removal from donor and transplantation to recipient. These products are classified as Medical Devices. They require extensive infectious disease screening and testing, with procedures which closely control good handling practices.  They require pre-market approval as they represent a substantial risk due to risk of spreading infectious agents. These products fall under the Center for Biologic Evaluation and Research (CBER) in the USA, and are classified in Europe as Class III devices requiring a substantial and reviewed device dossier, as they contain biologically derived materials. Minimally manipulated products do not require a PMA. A number of companies such as LifeCell sell products in this category, and a number of other companies are developing products in this area.

Tissue engineered implants represent a broad category of materials from those that are substantially donated allogeneic tissue with cells removed, to those products that are completely biologically based such as follicle and placental cell infusions.

Synthetic products are Class II devices, requiring PMA approval and good manufacturing practices in the USA, and the equivalent CE Mark and Class II approval in Europe.

Biologically-derived products are approved through the mutual recognition process in Europe as biological pharmaceuticals and require PMA approval in the USA, and manufacture to good manufacturing practice standards. These products are regulated by the CBER in the USA as biologics requiring a Biologics License Application.

See the complete report description, table of contents and list of exhibits at link.

Cell therapy is defined as a process whereby new cells are introduced into tissue as a method of treating disease; the process may or may not include gene therapy. Forms of cell therapy can include: transplantation of autologous (from the patient) or allogeneic (from a donor) stem cells , transplantation of mature, functional cells, application of modified human cells used to produce a needed substance, xenotransplantation of non-human cells used to produce a needed substance, and transplantation of transdifferentiated cells derived from the patient’s differentiated cells.

Once considered a segment of biomaterial technologies, tissue engineering has evolved into its own category and now comprises a combination of cells, engineering and suitable biochemical and physiochemical factors to improve or replace biological functions. These include ways to repair or replace human tissue with applications in nearly every medical specialty. Regenerative medicine is often synonymous with tissue engineering but usually focuses on the use of stem cells. 

Tissue engineering and cell therapy may be considered comprised of bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration. These often comprise a combination of biotechnology, medical device and pharmaceutical technologies. 

Researchers have been examining tissue engineering and cell therapy for roughly 30 years. While some products in some specialties (such as wound care) have reached market, many others are still in research and development stages. In recent years, large pharmaceutical and medical device companies have provided funding for smaller biotech companies in the hopes that some of these products and therapies will achieve a highly profitable, commercial status. In addition, some companies have been acquired by larger medical device and pharmaceutical companies looking to bring these technologies under their corporate umbrellas. Many of the remaining smaller companies received millions of privately funded dollars per year in research and development. In many cases it takes at least ten years to bring a product to the point where human clinical trials may be conducted. Because of the large amounts of capital to achieve this, several companies have presented promising technologies only to close their doors and/or sell the technology to a larger company due to lack of funds.

The goal of stem cell research is to develop therapies to treat human disease through methods other than medication. Key aspects of this research are to examine basic mechanisms of the cell cycle (including the expression of genes during the formation of embryos) as well as specialization and differentiation into human tissue, how and when the differentiation takes place and how differentiated cells may be coaxed to differentiate into a specific type of cell. In the differentiation process, stem cells are signaled to become a specific, specialized type of cell when internal signals controlled by a cell’s genes are interspersed across long strands of DNA and carry coded instructions for all the structures and functions of a cell. In addition, cell differentiation may be caused externally by use of chemicals secreted by other cells, physical contact with neighboring cells and certain molecules in the microenvironment.

The end goal of stem cell research is to develop therapies that will allow the repair or reversal of diseases that previously were largely untreatable or incurable.. These therapies include treatment of neurological conditions such as Alzheimer’s and Parkinson’s, repair or replacement of damaged organs such as the heart or liver, the growth of implants from autologous cells, and even regeneration of lost digits or limbs.

In a developing human embryo, a specific layer of cells normally become precursor cells to cells found only in the central nervous system or the digestive system or the skin, depending on the cell layer and the elements of the embryo that direct cell differentiation. Once differentiated, many of these cells can only become one kind of cell. However, researchers have discovered that adult body cells exist that are either stem cells or can be coaxed to become stem cells that have the ability to become virtually any type of human cell, thus paving the way to engineer adult stem cell that can bring about repair or regeneration of tissues or the reversal of previously incurable diseases.

Another unique characteristic of stem cells is that they are capable of self-division and self-renewal over long periods of time. Unlike muscle, blood or nerve cells, stem cells can proliferate many times. When exposed to ideal conditions in the laboratory, a relatively small sample of stem cells can eventually yield millions of cells.

There are five primary types of stem cells: totipotent early embryonic cells (which can differentiate into any kind of human cell); pluripotent blastocyst embryonic stem cells, which are found in an embryo seven days after fertilization and can become almost any kind of cell in the body; fetal stem cells, which appear after the eighth week of development; multipotent umbilical cord stem cells, which can only differentiate into a limited number of cell types; and unspecialized adult stem cells, which exist in already developed tissue (commonly nerves, blood, skin, bone and muscle) of any person after birth.

Source: MedMarket Diligence, LLC; Report #S520, "Tissue Engineering & Cell Therapy Worldwide 2009-2018."

Developmental Timescales

Tissue engineering and cellular therapy products take years of research and many millions of dollars (averaging about $300 million, according to some reports) before they make it over the hurdles of clinical trials and into actual market launch. More than one small biotech company has burned through its money too quickly and been unable to attract enough investment to keep the doors open. The large pharmaceutical and medical device companies are watching development carefully, and have frequently made deals or entered into alliances with the biotechs, but they have learned to be cautious about footing the bill for development of a product that, in the end, may never sell. 

For many of the products in development, product launch is likely to occur within five years. Exceptions include skin and certain bone and cartilage products, which are already on the market. Other products are likely to appear on the European market before launch in the United States, due to the presence of (so far) less stringent product review and approval laws in the European Union. 

Even when the products are launched, take-up will be far from 100% of all patients with that particular condition. Initially, tissue engineering and cell therapy products will go to patients suffering from cancers and other life-threatening conditions, who, for example, are unable to wait any longer for a donor organ. Patients who seem to be near the end of their natural lives likely will not receive these treatments. Insurance coverage will certainly play a key role as well in the decision about who receives which treatments and when. But most importantly, physicians will be selecting who among their patients will be treated; the physicians learn about the treatments by using them, by observing the patient’s reactions, and by discussing their experiences with colleagues. In other words, the application of tissue engineering and cellular therapy will progress in a manner similar to the introduction of any new technology: through generally conservative usage by skilled, highly trained physicians dedicated to providing their patients with the best possible treatment without causing them additional harm. 

The FDA put a slight dent in forecasts for obesity drugs, with a negative view (and decisions) in 2010 that it now seems to be backing away from.

Having forecasted the obesity market earlier this year and having taken a position that the FDA might well revisit its negative decisions on Contrave, Lorcaserin and Qnexa (especially if additional trial data is submitted to address specific concerns), we still hold that there will be substantial upside in obesity drugs (and devices) over the coming decade.

This is especially true for Europe which, at least in principle, is unaffected by FDA decisions. Below is our forecast of the obesity products market, by specific drug and device types, for Europe through 2019 (sales in $millions). 

Source: MedMarket Diligence, LLC; Report S835.

Wounds have been closed and secured through the use of suture materials since ancient Egyptian times. In the modern medical age, suture materials have evolved through a succession of stages from non-resorbable, to resorbable, to stapling devices. Sutures still represent the majority of products used for wound closure and securement, but their days of being the sole means to secure and seal wounds is in decline.  Nonetheless, sutures (and other mechanical closure) represent a traditional "gold standard" that all advanced wound closure products must measure up to, whether alone or as products used adjunctively with other closure methods to optimize wound management.

There are six main categories of closure and securement devices:

• sutures, staples, and other mechanical closure devices
• medical tapes
• hemostats
• fibrin and other sealants
• high-strength medical adhesives
• post-surgical adhesion prevention

Source: MedMarket Diligence, LLC; Report #S180.

From "Worldwide Spine Surgery: Products, Technologies, Markets & Opportunities, 2010-2020", Report #M520, published 2011 by MedMarekt Diligence:

Vertebral compression fractures result primarily from osteoporosis and the consequent weakening of bones, including those in the spine. VCFs can result in tremendous back pain both in the short and long term. Because the injured vertebra is compressed and loses height, kyphotic deformity of that particular vertebra and the spine as a whole often results. Kyphosis in and of itself can produce pain long after the vertebral compression fracture has healed. As discussed earlier, several conditions can lead to osteoporosis, including estrogen deficiency, multiple myeloma, radiation therapy, and natural aging. Bones weakened either due to the primary disease process or as a result of treatment of such diseases are more prone to fracture. Common sites osteoporotic fracture include the spine, hip, and wrist.

The traditional treatment for VCFs is conservative care with back braces, bed rest, and analgesic medications for alleviating pain. Although given time the fracture eventually heals, the vertebral body remains in a collapsed, compressed state. This can result in prolonged pain, impaired function, and decreased activity. Additionally, bone and muscle loss resulting from a lack of activity can make recovery even more difficult, leading to the so-called ‘downward spiral’ of vertebral osteoporosis.

In recent years, two minimally invasive procedures have been introduced to treat VCFs: vertebroplasty and kyphoplasty. The procedures are very different, in that vertebroplasty is designed to stabilize the break, while kyphoplasty attempts to both stabilize the break and bring the collapsed vertebra back to its original height. 

Companies with products in vertebroplasty and/or kyphoplasty on the market or under development include: Alphatec, ArthroCare, AscendX, Benvenue Medical, Biomet, BoneSupport, CareFusion, Cook, DePuy Spine, Dfine, Integra Spine, Lafitt, Medtronic, Orthovita, Osseon Therapeutics, Signus, Sintea, Skeltex, Soteira, Spine Wave, SpineAlign, Stryker, Synthes, Tecres, Teknimed, Vexim.

Kyphoplasty is currently the bigger market, but trends in procedure volume, pricing and unit sales are causing the gap in global market between kyphoplasty and vertebroplasty to disappear during the forecast period.

As the practice and the market for surgical sealants, glues, wound closure and anti-adhesion evolves, a marked shift is taking place that is moving caseload and market from traditional wound closure products (sutures, staples, mechanical closure, tapes) to advanced wound closure products (hemostats, fibrin and other sealants, high-strength medical adhesives, and post-surgical adhesion prevention).

Below is illustrated the change in the percentage of the total market for wound closure and securement products.

Source: MedMarket Diligence, LLC, Report #S180, "Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2008-2015".

This is not a post about me or my business.  This is about being human and recognizing, in all of the people around us, what it is to be human.  We are all human.

On Saturday, October 1, while on my way with my wife and kids to go to the movies, we encountered a man, off his bike and down on the side of the road, who had suffered, as we found out later, a massive heart attack.  He had what is called a "widow maker" heart attack, resulting from a total occlusion of his left anterior descending coronary artery. Another passerby, a bicyclist like the man down but (as I learned) was not with him, had encountered the man down moments before and look a bit rattled, seeing the seriousness of the situtation, but not seeming to know what to do.

My father was a surgeon, my uncle a pediatrician.  I considered medicine as an undergraduate but found I didn't have the cutthroat temperament that was prevalent among pre-meds, nor did I really have the drive to pursue the career. I was also eminently distracted by a lot of other great science that was taking place in molecular biology and genetics in the early 1980s.  So, after college, I traveled down a road that included healthcare, commercial biotechnology labwork, biotech business development and ultimately market analysis of medical technologies. I was fascinated by the idea of applying science to specific, targeted applications -- diagnostics, therapeutics. That road took me into healthcare, but in a role that is at arm's length from people, the actual recipients of healthcare.

The man down is younger than me. I'm 51.  Aside from being unconscious, he looks like he is in pretty good shape. My guess is that he could be in his mid or late-30s.  (I learn later that he is actually 49.)  With the mountain bike, his helmet on, sunglasses on, lying on his back on the slope by the sidewalk --  he looks like he is just resting from his ride. But as the other biker recognized, the man down is not resting, he's unconscious.

Twenty years ago, I worked at Parkland Hospital in Dallas, close to the University of Dallas, where I got my bachelor's degree. I worked there to gain exposure to the front line of medicine. Parkland is a large county hospital (where JFK was brought after Dealey Plaza) that encounters everything in metropolitan medicine from major to minor trauma and every type of ailment, injury and disease. Its ER alone is larger than most hospitals, even at big cities. As an "emergency technician" -- slang for "do everything unappealing that needs to be done in the ER", from clean up to "take this poor soul to the morgue" -- I encountered a lot of medicine that was perfectly suited to showing me the hardcore reality of medicine. It neither validated nor rejected my view of medicine as a career, since for whatever reason I felt as if I already knew this was the way it was. People live, people die, naturally or not, and all of them happened there, from the poor old emaciated woman with jet black hair (dyed probably out of vanity), whose family brought her, in advanced stages of metastatic cancer, to die in the ER without pain, to the poor blue collar worker who suffered a massive heart attack at the end of his otherwise unremarkable day. I saw those who were beyond help as often as those who were pulled from the abyss by underpaid nurses and exhausted ER docs who just did the right thing when it was necessary.

I pat him several times on the shoulder and call to him, "buddy, are you OK, can you hear me?". No response.  I check his pulse.  I feel two, maybe three beats that are feeble and not convincing. The beats stop. I pull off his sunglasses. That hits me hard, since his eyes are looking at something, or nothing, that isn't here anymore. I realize that I've seen this before and I start to tense (this man is close to the end).  I put my ear to his chest to hear something, anything. Nothing. At this point, I hear my mother urging me to do the right thing no matter what. I just start in without much thought and, in any case, I feel as though I'm operating purely on instinct anyway.

I am thinking, this man is young -- younger than me -- I have no doubt that he has a young wife and young kids.  My eyes well up as I think, someone loves him, someone depends on him, I have to do something, I have to try. "Call 911" I yell, knowing there are other people behind me, and I hear someone respond that they're on it. I pull off his helmet (thinking, it's too tight, the strap must be hurting his ability to get air), he's in the bushes on a slope, let's get him down on the sidewalk. I worry that his head, which lolls so freely forward and back, will hit the pavement. I call to the other bicyclist to hold the man's head, he does, and I lay him down.

At that point, it is really a blur as I do everything I can, calling upon everything I have learned from training years ago, from references to CPR I have read recently (not realizing how "relevant" they are), to my instincts. He needs oxygenated blood. How long has he been down? He's warm, not long, but it's also hot today. Who knows? I give three to four breaths to make sure there's fresh oxygen in his lungs. The air comes back in a groan from him (my emotions say he's alive, but my logic tells me it's just air coming back over the vocal cords). He needs compressions, mostly compressions. I start doing the compressions, knowing that it's the center of the sternum, above the xyphoid process and that it requires deeper compressions than my instincts might suggest.

Time is passing faster than I can realize. I honestly have no idea how long I have been at the compressions. Five, ten minutes, more? Sirens, fire trucks, Orange County Sheriffs, suddenly there are MANY people here. An EMT asks, Are you OK? Can you continue? I need to get set up, he says. I'm fine (I can't see how I would stop until they told me to). He says, OK, just keep going a little faster, a little deeper, so I do.

Eight years ago, in the middle of the night, I had a deep chest pain that didn't resemble any minor ache, pain, or gas bubble I had ever had. I called my doctor, got checked out. At 43 years old, I had two coronary arteries that were nearly 90% occluded.  An angioplasty and a stent brought me back to my wife and kids and changed my definitions of what was important from then on.

I am relieved to have all of these professionals take over, with their training, experience, and technologies.  But at the same time, I worry about this poor man, who I have come to have such a vested interest in, and whether they will absolutely do everything they can to get him back.

He is defibrillated two, three (?) times, arms flying up in reaction to the jolt. I wait for some kind of response that is not a simple reflex, a reaction.  An EMT tells me he's in v-fib (ventricular fibrillation) -- I ask if that is in any way a good sign, but he says no, not really. Neighbors have now arrived, recognizing me or just drawn by curiosity to this event. I tell those I know that this doesn't look good. I try not to break down. This poor man. His poor family.

I realize, after giving my story and contact details to police that it is time for me to leave. The man is being put on a stretcher, loaded into the ambulance.  An officer comes to me, shakes my hand and says thank you, he has a chance. I am startled. He says there is a pulse, he may yet make it.

My wife and kids are in the car across the street, I need to go to them. (I learn that my wife wanted to make sure 911 was called, knowing that cell phones are sometime unreliable in giving precise locations, so she drove to a neighbor's house, burst in and did so. She will always do the right thing.)

I see a woman arrive at the scene, very distraught, she must be his wife. I want to comfort her, but it is all so chaotic, uncertain. I am so afraid for her future and his.

I have no idea who he is. I've never seen him before.  But that doesn't matter.  He's human. I'm human. I have no choice but to try and help him.

My first instinct after telling people about this is to tell them, take a course in CPR. Get certified. Someday you just might need it and you will never regret that at least you did your best.

He is still in the hospital.  His fate is uncertain and he may not yet make it. All I know is that, if I was not there and did what I did, his fate would indeed be certain.

The challenges in the treatment of obesity are in providing practical, long-term solutions to a condition that is growing rapidly and is associated with numerous co-morbidities that include diabetes, hypertension (and other cardiovascular diseases), gastroesophageal reflux disease (GERD), osteoarthritis, fatty liver disease, obstructive sleep apnea, and cancer, among others.

Obesity is most commonly addressed, from a clinical solution, in device- and non-device-related bariatric surgery and a very limited number of drugs. Roux-en-Y and other gastric bypass procedure volumes have seen steady increases over the past few years as these procedures have been aggressively marketed and third party reimbursement has become more common.  Obesity device sales (lap-band and others) have grown, and will continue to grow, steadily.

As with most surgeries, however, there are morbidities associated with the procedures, whether or not devices are employed and long-term success has not been high enough to displace demand for pharmaceutical solutions.  Development of pharmaceuticals for obesity has been aggressive, but fraught with uncertainty in the regulatory process that, until only in mid-2011, seemed to make approval to be a moving target, if not unreachable.

Beyond the revived approval process now in play for drugs by Vivus, Orexigen, and Arena, pharmaceutical development in the field of obesity is focusing on several major areas:

• Melanocortin receptor system
• Cannabinoid receptor agonists
• GLP-1 analogs
• Methionine aminopeptidase 2 (MetAP2) inhibitor
• Appetite suppression drugs (Arena's lorcaserin, NeuroSearch’s Tesofensine, Shionogi's Velneperit)
• Malabsorption drugs
• Satiety drugs
• Combination drugs

We track the market for all obesity drugs and devices on the market and in development in our Report #S835, "Products, Technologies and Markets Worldwide for the Clinical Management of Obesity, 2011-2019."