Lab Soft News

Organizational Innovation with a Political Overlay; Lessons from Microsoft

An elusive goal for many companies is the quest for innovation. It's not merely a question of buying talent. It's frequently more about establishing a corporate culture that fosters new ideas and products even at the risk of cannibalizing its current product line. In my opinion, innovation is a quality that is sorely lacking in the U.S. EMR market today, prompting the comment that Epic sells well because its the best of a bad lot. A recent article analyzing Microsoft's lack of an innovative spirit by a former executive of innovation caught my eye (see: Microsoft’s Creative Destruction). Below is an excerpt from it:

Microsoft has become a clumsy, uncompetitive innovator. Its products are lampooned, often unfairly but sometimes with good reason. Its image has never recovered from the antitrust prosecution of the 1990s. Its marketing has been inept for years....While Apple continues to gain market share in many products, Microsoft has lost share in Web browsers, high-end laptops and smartphones....It first ignored and then stumbled in personal music players until that business was locked up by Apple. Microsoft’s huge profits — $6.7 billion for the past quarter — come almost entirely from Windows and Office programs first developed decades ago. Like G.M. with its trucks and S.U.V.’s, Microsoft can’t count on these venerable products to sustain it forever. Perhaps worst of all, Microsoft is no longer considered the cool or cutting-edge place to work. There has been a steady exit of its best and brightest. What happened? Unlike other companies, Microsoft never developed a true system for innovation. Some of my former colleagues argue that it actually developed a system to thwart innovation. Despite having one of the largest and best corporate laboratories in the world, and the luxury of not one but three chief technology officers, the company routinely manages to frustrate the efforts of its visionary thinkers.

For me, innovation within an organization results from a combination of two factors. It's critical to both recruit innovators into key positions and also develop an organizational culture that embraces innovation and change even when the early consequences of change may be disruptive and look like a setback. Recall the "S-shaped curve" that governs all early deployments of new technology (see: Can an Electronic Medical Record Cause Harm to Patients?). There is almost universally an early decrease in efficiency following such deployments because of the need for training with the new technology and the disruptive effects when previous routines and processes are changed. Getting past these early change effects allows the organization to reach the rapidly-ascending part of the curve and rapidly gain efficiency until the curve flattens out and it's time to deploy new technology again.

As noted above, having innovative thinkers in the employment of an organization is only part of the equation. Recall that such individuals are also immersed within an organizational and political context as well. Some organizations do not accept change readily, do not reward risk-taking, and foster short-term thinking and the bottom-line. Some managers, or even perhaps most of them, jealously guard their own budgets, local power, and product lines. Such managers can "frustrate the efforts of its visionary thinkers" by suppressing new ideas and products that do not enhance the success of their own units. Sometimes the only way around such impediments is to nurture new technology in a "skunk-works environment" that is separately financed but protected from political attacks by other jealous managers in the company.

Patient Symptoms Inadequate Way to Diagnose Ovarian Cancer

One of the challenges of malignant neoplasms like ovarian and pancreatic cancer is that the early signs and symptoms are either absent or nonspecific. A recent article that discussed this problem for ovarian cancer is not encouraging (see: Symptoms Poor Indicators Of Ovarian Cancer, Study Finds). Below is an excerpt from it:

Only about 1% of women who experience symptoms of ovarian cancer, such as persistent bloating or pelvic pain, actually have the cancer, according to a study published Thursday in the Journal of the National Cancer Institute.... Lead author Mary Anne Rossing...said, "What this (study) suggests is that it's going to be hard to move the diagnosis of ovarian cancer forward." Many medical societies recommend the use of these symptoms to aid early detection of ovarian cancer, but the study found no evidence that the symptoms could lead to earlier detection. About 14,000 women die from ovarian cancer annually in the U.S., and it is estimated that one in 2,500 women has the disease without knowing it. Experts do not advise routine ovarian cancer screening for the general population because of a high rate of false positives and risk for unnecessary surgeries....The study noted that 100 women who report having symptoms would need to be examined to detect one cancer. It also found that among the women who did not have cancer, 6% had persistent symptoms. However, because the disease is rare, these women are unlikely to have it, the study said. The findings support "a cautious approach to the use of symptom patterns to trigger extensive medical evaluation for ovarian cancer," the researchers wrote.

This is not good news. The conclusion is that only a very small percentage of women who experience the symptoms of ovarian cancer actually have the disease. If you can't depend on the appearance of symptoms to prompt physician visits by patients with the disease, what's left? Routine imaging for screening purposes is not an option -- the disease does not have a sufficiently high prevalence to justify this approach. It seems to me that the only answer is the development of an effective IVDMIA (i.e., biomarker panel) to screen for the disease. About two years ago I posted a note about a multiplex test to screen for ovarian carcinoma (see: Encouraging Results from LabCorp/Yale Multiplex Lab Test for Ovarian Cancer). This created a firestorm of criticism regarding lack of FDA approval for the test (see: F.D.A. Says Cancer Test Failed to Get Its Approval).

It appears that little progress has been made since that time in the development of screening tests for ovarian cancer. Here's a quote from the American Cancer Society web site:

CA-125 is a protein in the blood that is higher in many women with ovarian cancer. The problem with this test is that conditions other than cancer can also cause high levels of CA-125. In addition, someone with ovarian cancer can still have a normal CA-125 level. When a CA-125 level is abnormal, many doctors will repeat the test....The doctor may also consider ordering a transvaginal ultrasound test. In studies of women at average risk of ovarian cancer, these screening tests did not lower the number of deaths caused by ovarian cancer. This is why transvaginal sonography and the CA-125 blood test are not recommended for ovarian cancer screening of women without known strong risk factors....Ways to improve ovarian cancer screening tests are being researched. Hopefully, further improvements will make these tests effective enough to lower the ovarian cancer death rate.

Lab Soft News Named One of the Fifty Top Healthcare IT Blogs

I recently received an email from James J Atkinson, The Health Sensei, telling me that he has chosen Lab Soft News as one of the top fifty healthcare IT blogs (see: Top 50 Healthcare IT Blogs). The picks are categorized (e.g., CIO and IT Technician Blogs, HIT News & Opinion Blogs, etc.) rather than displayed in rank order. Lab Soft News falls into the second bucket. The recognition is well appreciated but check out the others -- it's a great list. Take some time to savor them and bookmark the page for later reference.

Some Salty Facts Keeping to a Healthy Diet

I have come to view certain common food ingredients (e.g., salt, sugar, and fat) as "toxic" in the sense that they should be consumed only in small quantities. The current recommendation regarding salt consumption, calibrated in terms of sodium, is to consume less than 2,400 milligrams (mg) per day. This amounts to about 1 teaspoon of table salt daily. Understanding that salt is a flavor enhancer, I have personally been looking for ways to reduce my dietary salt input but not to the point where my meals become tasteless. A recent article about dietary salt contained some very interesting tidbits of information (see: On the Plate, a Pinch or a Pound?). I list them below:

• Packaged foods are an easy target, often so gunked up by chemicals that it takes a pile of salt to get any flavor at all. As for restaurants, the salt initiative seems to be aimed at fast-food joints, but salt plays an important role in nicer kitchens, too — the kind where actual human beings cook actual food.

• When a chef cooks in [a restaurant], salt is only one of the many tools — along with garlic or citrus or fresh herbs, say — she can use to build flavor. But if you’re stirring a huge vat of goo in an industrial food factory a mile below the earth’s surface, salt is one of the only tricks you have, so you have to use it a lot.

• Katz’s [Delicatessen of New York's] justifiably famous corned beef sandwich, with mustard but only two of the six pickles the counter guy gave me (along with his number), came to a truly remarkable 4,490 milligrams of sodium. That’s about two whole days’ worth in one sandwich, nearly the equivalent of 10 McDonald’s hamburgers.

So where does all of this leave me personally? First of all and to the extent possible, I will try to avoid most prepared and packaged foods except perhaps those that make specifically mention attention to reduced salt. Obviously, it's a good idea to read the ingredients on all labels. Secondly, I am going to view ketchup, mustard, and other condiments with deep suspicion. Ketchup has 150-200 mg of sodium in 1 Tbsp and who uses only 1 Tbsp of ketchup on a hamburger? Thirdly, I will continue to cook with a little salt but, as the top chefs recommend, add small amounts periodically when cooking to bring out the flavor. Lastly and pertaining to corn beef accompanied by dill pickles, I am still thinking about this one.

Attributes of 21st Century Healthcare Delivery According to Sir Muir Gray

The Dark Daily posted an article recently discussing the attributes that colored the practice of medicine and healthcare delivery during the last century and compared them with the drivers for this century. These ideas were offered by Sir Muir Gray to the attendees at the Frontiers in Laboratory Medicine (FiLM) conference that took place in Birmingham, England (see: Pathologists and Clinical Lab Professionals Urged to Think in “21st Century” Terms). Sir Muir Gray is the Chief Knowledge Officer for Great Britain’s National Health Service (NHS) National Library for Health.

Here's a key quote directly from the article: “In 20th Century Medicine, quality was the term most commonly used to describe the level of service,” explained Gray. “For 21st Century Medicine, value will be more important than quality.” Gray believes value is the term which communicates the worth of a specific health service, because value carries within it the attributes of quality, while addressing the other attributes that convey all the value that meets the expectations and needs of a patient.

Below is a table, copied directly from the article, with a head-to-head comparison of the descriptors of the  healthcare system of the past century and those of the century we have just embarked on:

20th Century Healthcare

1. Doctor centered    
2. Patient as passive complier    
3. Hospital    
4. Bureaucracy    
5. Driven by finance    
6. High carbon    
7. Focused on effectiveness
8. Challenges met by growth
   

21st Century Healthcare

1. Patient centered
2. Patient as co-producer
3. System
4. Network
5. Driven by knowledge
6. Low carbon
7. Focused on value, eliminating waste
8. Challenges met by transformation

I am having a few problems with the words "quality" and "value" because, as noted above, quality is a value. However, if you look at item #7 in the two lists above, it may be possible to achieve clarification. We are moving from an era of effectiveness (doing things right) to an era of efficiency (doing the right things). Both are components of quality care. In addition, many of the other comparisons above are also of great interest to me: Patient as passive complier vs. Patient as co-producer; Driven by finance vs. Driven by knowledge; Challenges met by growth vs. Challenges met by transformation.

I want to return to some of these ideas in the near future, particularly the idea of the patient as a co-producer of care and of improved outcomes. This change is powered by access to knowledge by the healthcare consumer/patient, often via the web. I also believe that this driver will be one of the key elements in reducing the cost of healthcare because, obviously, the consumers/patients do not charge for the services and value that they co-produce for themselves.

More on Reaching Young Males with Public Health Education Messages

In a recent note, I commented on the television viewing habits of young adult males and suggested some ways in which public health messages could be developed in order to reach them more effectively (see: “The Mind of the Young Adult Male and On-Line Health Education) A reader of this blog, Ajit Ailes, responded with the following comment:

These males are also in the earliest stages of accepting mortality. If we look at Elisabeth Kubler-Ross's staging of the acceptance of dying in terminal patients, these young men are in the stage of denial. They are generally healthy and feel immortal. So why would they worry about health care? Maybe the serious issues of the day could be woven into a video game or cartoon as part of the plot rather than as a separate program. A good example of this is "The Simpsons" cartoon series which has discussed some very serious philosophical issues that the "real" programs wont touch. Take a look at this series if you haven't already seen it. Another possibility - some decades ago, there were always informational short films/features shown before the main movie. Maybe we should start doing the same thing again, addressing serious issues. This guarantees a captive audience that might be receptive to serious, but concise, discussions of the issues.

I believe that the idea of catching the attention of young adult males with public health messages embedded in short films before the featured presentation in movie theaters just won't fly. The customers have paid to see the main event and don't want to be distracted. However, Ajit's idea of weaving public health themes into the plot elements of cartoon series like "The Simpsons' has real merit. However, The Simpsons' is so unique that it's probably not a good idea to extrapolate from the experience of this show. The key question, then, is how to interest the writers of other shows to adopt this approach on a broader basis.

I do reject the idea of "product placement," which is to say, paying the producers of a TV series to sneak in plot messages about sexually transmitted diseases or other public health issues. Perhaps a more successful approach would be for professional medical societies such as the College of American Pathologists (CAP) to make overtures to the executives in the video game, TV, movie industries to feature health issues in their plots. They could then provide physician experts from among their ranks to assist the producers of these media in getting the message right. My concern in such relationships is that there will be a large understanding and communication gap between the various parties. Such relationships, I am sure, already exist in the form of paid expert consultants who are hired by the media producers to avoid obvious factual errors.

Further Consideration of the Definition for Personalized Medicine

I have been grappling for many months with an acceptable new definition for personalized medicine and recently raised this topic again in a note (see: Term "Personalized Medicine" More About Business than Healthcare Delivery). Dr. Brian Jackson of ARUP Laboratories frequently comments on my notes and provides remarkable new insights. His most recent comment is no exception. I reproduce it below in its entirety:

I think you're being too narrow when you define personalized medicine as targeted therapy. Though you're much more on the right track than the vast majority of biomedical folks who think it means simply performing whole genome analyses on everyone. Given that we're pathologists, how about we define personalized medicine in terms of the information integration necessary for patient care? The two ends of the spectrum in my mind are population medicine and personalized medicine. Population medicine is essentially EBM. It gets criticized for being cookbook, but the fact is that there is important information value in studying large groups of patients at a time -- think where we'd be if randomized clinical trials didn't exist. At the other end of the spectrum is personalized medicine, i.e. acquiring and integrating more and more patient-specific information. I firmly believe the sweet spot will be when we figure out how to properly balance and take advantage of both population-based information and personalized information and apply that to individual patients.

The problem that I have with Brian's idea, incorporating the notion of personalized medicine with population medicine, is that I don't like the use of the term personalized at all. It's so subject to misinterpretation that I want to abandon it entirely. However, Brian's comment got me thinking that the alternative term that I have been using for personalized medicine, targeted therapy, is too narrow. It fails to take into consideration the use of sophisticated diagnostic tests that I have been constantly emphasizing in Lab Soft News. So, in the process of crafting an expanded definition for personalized medicine, let's start with targeted diagnostics and therapeutics, understanding that many of the emerging biotech drugs would be far less useful if unaccompanied by companion diagnostics. Now, let's build on this work-in-progress by also capturing Brian's ideas about the criticality of integrated care and evidence-based medicine (EBM). They incorporate the experience gained by treating large patient populations and large clinical trials. Here is our new, and complete for now, definition for your consideration:

Personalized Medicine: targeted diagnostics and therapeutics that incorporate the knowledge gained through evidence-based medicine as well as the individual and unique characteristics of the patient being treated.

Distinguishing Medical Errors from Negative Outcomes

I have recently become interested in the topic of overdiagnosis with special reference to the practice of surgical pathology (see: Confusion Caused by Conflating "False Positive" and "Overdiagnosis" in Breast Cancer, Continuing Discussion of the Various Types of Diagnostics-Driven Cancer Overdiagnosis). I will take the term overdiagnosis to mean "overcalling" a diagnosis. Stated another way, the pathologist unconsciously drifts toward a more serious diagnosis on the basis of her or her training or perhaps unconsciously to avoid the error of undertreatment. Overdiagnosis sometimes leads to overtreatment but I suspect that undertreatment is more likely the cause of medical malpractice suits than overtreatment. I recently encountered an article discussing the extent to which patient safety is taught to medical students (see: Patient Safety: Conversation to Curriculum). The passage quoted below caught my eye:

Through such sessions, students can learn how medical errors are defined and how to tell an error from a negative outcome, said Dr. Melissa A. Fischer, an assistant professor of medicine at the University of Massachusetts Medical School. As she emphasizes to her students, “bad things can happen even when everything is done right.”

Hmmm. This article indicates that medical errors are different than negative outcomes and can be distinguished from them. I don't know the medical literature in the area of patient safety so I will need to "wing it" in this discussion. I will take negative outcome to mean that the patient's condition gets worse during treatment because of the natural history of the disease or because of unavoidable sequelae of the treatment itself. You may have all heard the old adage: the operation was a success but the patient died. I will take a medical error to mean that a discernibly wrong step or action was taken during treatment and the patient suffered from it.

I believe that most physicians, and most patients, are predisposed to treating a disease (i.e., take some overt action) rather than following the course of the disease, thereby postponing treatment until the condition worsens. The latter process is sometimes called watchful waiting. This is a common approach when early prostate cancer is diagnosed in older men. Nearly all therapeutic interventions (e.g, surgery, drug treatment) can lead to some negative outcomes. For example, most drugs have both known and unknown side effects. Some people never wake up from general anesthesia.

What are the negative outcomes of the clinical monitoring of a known disease, which is to say watchful waiting? One of them is that the patient is psychologically uncomfortable living in an untreated state. Another is that the disease progresses so rapidly that it quickly reaches an untreatable stage and the patient would have been better off having been treated earlier. This latter case is probably rare, given the fact that watchful waiting is reserved for the more indolent diseases and also because of the predisposition of most physicians is to actively treat most of their patients. However, I need to add that watchful waiting may soon become a more attractive clinical scenario as the sophistication of serum biomarkers and medical imaging improves. In other words, as the efficiency and efficacy of diagnostics improves, the penalty for observing an untreated disease diminishes.

Major HIPAA Breach in Las Vegas Hospital Investigated by FBI

There have always been rumors circulating in the hospitals where I have worked that unnamed clinical personnel were on the payroll of the medical malpractice lawyers in town. They would phone the firm whenever they learned that various types of trauma patient have been admitted to the hospital or when some medical error had occurred or been detected. Attorneys from the firm would then visit the patient and drop a business card. Obviously a very serious breach of hospital and patient confidentiality, if these rumors were true. Better documented, however, is the fact that most breaches of patient confidentiality that occur in hospitals are inside jobs.The are committed by hospital employees who have ready access to patients' physical or electronic medical records, at least in the units where they work. I recently came across an a article about a serious HIPAA breach at University Medical Center, Las Vegas, where an investigation by the FBI is now underway. Below is an excerpt from it (see: UMC admits to prolonged patient privacy leak):

University Medical Center officials said Monday that personal information of traffic accident victims was likely leaked from its trauma center for more than three months, and stopped only after the Las Vegas Sun told the hospital about the breach. The hospital’s statement was the first acknowledgment that the leak of patient data was more widespread than it had previously said, and closer in time to what the Sun had reported.The breach had apparently been going on for months....The FBI is investigating because such leaks of patient data would violate the Health Insurance Portability and Accountability Act, better known as HIPAA, a federal law that guards patient privacy in health care facilities. UMC waited almost a month to notify patients about the leak of their personal information, and that of people who accompanied patients to the trauma center. UMC is offering the victims free credit monitoring services for a year, although there have not been any reports that the data have been misused....A source in the medical community had provided the newspaper with the documents. The source is several degrees removed from the leak at UMC and did not know exactly where the documents came from....Congress recently increased the penalties for HIPAA violations. A person who violates a patient’s privacy with the intent to sell information can be fined up to $250,000 and imprisoned for up to 10 years. The FBI launched an investigation into the leaks after the Sun told hospital officials Nov.19 that it had come in possession of “face sheets,” the cover sheets that contain personal information about each case, such as Social Security numbers, birth dates and accident details and injuries sustained....

A few aspects of this case strike me as being quite odd. The first is that the hospital personnel waited a month to notify the patients about the security breach. I am sure that their excuse is that they were investigating the incident but this strikes me as too long a wait. The second is that the newspaper information source is described as being "several degrees removed from the leak at UMC and did not know exactly where the documents came from." My guess, on the basis of this hint, is that it may be disgruntled employee of a local law firm who was poking around in some locked files. The third point is that the hospital is offering the "victims" free credit monitoring services for a year. This strikes me as a slightly disingenuous move on the part of the hospital executives. Certainly credit card fraud is on the mind of many consumers and patients these days. However, there are many easier ways for criminals to get their hands on social security numbers than pilfering face sheets of medical records. My sense is that whoever was behind this crime had a more lucrative goal in mind than buying video game at the local Wal-Mart through identity theft. Make note of the fact that the hospital information leaks occurred in the hospital trauma center.

The Mind of the Young Adult Male and On-Line Health Education

Previously discussed here has been the topic of on-line public health education and the use of smartphones as efficient channels to reach the young adult population (see: Placing Public Health Announcements on Google as Paid Ads, Seeking Solutions to the Chronic Disease Epidemic, Making e-Health Information Accessible with Smart Phones, The Mobile Web and the Future of eHealth). This approach is particularly relevant for messages relating to sexually transmitted diseases (STDs) such as Chlamydia. It is for this reason that I paid close attention to a recent article regarding the adult male television viewership, or rather the lack thereof, of Conan O"Brien (see: O’Brien Undone by His Media-Hopping Fans). For those of you who distance themselves from popular culture, O'Brien recently ended his brief stint as host of NBC's "The Tonight Show". Below is an excerpt from the article

But to NBC’s surprise and disappointment, Mr. O’Brien fell behind his predecessor, Jay Leno, even among those 18-to-34 viewers, the group expected to be his core constituency....“The 18-to-34 group is so difficult to attract and the lower half, 18 to 25, is the hardest of all,” said [the president of a research firm]. Compounding the problem, said a senior research executive for another company, was the fact that Mr. O’Brien was especially appealing to young men. “And that group doesn’t watch television very regularly,” said [an unnamed executive]. Instead of watching Mr. O’Brien most nights..., those young viewers have been watching everything from similar shows like “The Colbert Report” on Comedy Central, to cartoons on the “Adult Swim” franchise on the Cartoon Network, and the ever-present array of sports and sports news on ESPN and its sister channels.

Every generation believes that one ones following it is going to the dogs. I will try to avoid this trap but merely reinforce the observation made above that U.S. men aged 18-34 spend much of their idle time watching cartoons and sports on TV and browsing the web. I would also add video games to this list. I assume that many of you already know this. In general, this segment of the population is quite healthy and only infrequently uses healthcare services. Most of them will mature into older adult males who will also watch sports events, perhaps lose their taste for cartoons, and also ignore their health. We need to invest more of our public heath education resources, meager as they are, in developing channels of communication with the male population, both young and old.

For a start, I would suggest spot public health announcements during major sports events broadcasts. I know, I know. This is prime television viewing time and expensive. Perhaps there is some opportunity to wedge public service announcements into some of these breaks relating to STDs and early detection of heart disease, diabetes, and hypertension. Or better yet, perhaps we could get some of these cartoon studios to develop short videos with a light touch about these topics for posting on YouTube.

Term "Personalized Medicine" More About Business than Healthcare Delivery

I have always had a sense of vague unease about the use of the term personalized medicine because I never quite understood what it meant. I also quickly learned that it was subject to misinterpretation by healthcare consumers and patients. For example, I have heard many of the latter define it as healthcare delivery that is tuned to their special and personal needs including, for example, the quality of the hospital food. I much prefer, as a substitute, targeted therapy which to me refers to the development of specialized biotech drugs that have the capacity to kill malignant cells without harming the patient host.

Mr. HIStalk articulated the basis of my discomfort with the term in a  recent brief note. As he correctly points out, it's a mere marketing slogan designed to attract investors to biotech stocks but not accomplish much else. Below is a short quote from his note:

Stanford Hospital and Clinics is involved with the Personalized Medicine World Conference, running now in Mountain View, CA (see: Silicon Valley to host conference on 'personalized medicine'). Attendees were “investment bankers, investors, attorneys, accountants and entrepreneurs,” so that pretty much says all you need to know about the business aspects of US healthcare.

Putting all of this together, the term personalized medicine should be viewed as an adverting and marketing term, which is defined in the following way: ...short, often memorable phrases used in advertising campaigns. They are claimed to be the most effective means of drawing attention to one or more aspects of a product. A key element of medical science is that terms need to be concise, understandable, and immutable. This avoids errors and harm to patients. A marketing program and the phrases associated with it, on the other hand, are designed to avoid clarity and precision. The goal is to lull the potential buyer of stocks or investor in "personalized medicine" companies into a comfort zone. He or she needs to feel good about companies but not quite understand what they do to make money.

Where Do We Go from Here in Healthcare Reform?

I posted a recent note about the abrupt reversal of fortune of healthcare reform based on the recent election of a new senator from Massachusetts (see: Healthcare Reform and The Pressing Need to "Explain" the Proposed Legislation to the Average Joe). L.Needham, in response, posted the following comment:

[Y]our thoughts and ire are well placed. Moreover, as is your style, you admirably refrained from the perilous fields of overt political opinion....The irony of this 'situation' is thick; so is the comedy....[S]tatements regarding a need of a better explanation to the public about the bills contents are 'now' what some proponents are calling for ....However, the guise of 'back-to-basics' is horrifying in its intent. What it says to me is similar to your own expressed views: that without the majority 'bully' leverage, Washington will now how to revert to 'previous' 'basic' practices of exponential back-scratching, steroid-enhanced pork enrichment, and 5-digit pages of legislative bargaining contents...simply to strive to create a legislation that might pass....The issues related to healthcare are so layered, so wide-reaching, that the last thing needed in its discussion is having to make promises across the board in hopes of creating something complex enough that everyone thinks that they're ok with the bill...and no one being able to assess its true meaning.

Keep these thoughts in mind and now take a look at the opinion of David Brooks of the New York Times regarding this setback to healthcare reform (see: Politics in the Age of Distrust):

Instead of building trust in government, the Democrats have magnified distrust. The country already believed Washington is out of touch with its core concerns. So while most families were concerned about jobs, Democrats in Washington spent nine months arguing about health care. The country was already tired of self-serving back-room deals, so the Democrats negotiated a series of dirty deals with the pharmaceutical industry, the unions and certain senators. Americans already felt Washington doesn’t understand their fears and insecurities. So at the moment when economic insecurity was at its peak, the Democrats in Washington added another layer of insecurity by threatening to change everything at once. Instead of building a new majority, the Democrats have set off a distrust insurrection (which is not the same as a conservative insurrection). Republicans are enraged. Independents are furious. Democrats are disheartened. Health care reform is brutally unpopular. Even voters in Massachusetts decided it was time to send a message.

We are now faced with the national leadership of a president who was viewed by many people, when elected, as a man of the people and a unifier, despite a rarefied set of academic credentials. He leads a party with the total and unwavering support of the labor unions which represent, in part, the rapidly diminishing blue collar class. With the goal of reforming healthcare, he has tripped off a "distrust insurrection" among a broad swath of the population including many of the people who felt that he was representing their best interests. The process has also revealed, in an attempt to pass a massive and comprehensive healthcare reform bill, that congress is a one-trick pony. It only knows how to pass complex legislation using special deals and large concessions to lobbyists with bags of money.

According to Brooks, there are four bad options facing congress; listed in parentheses are his examples of how each option might be executed: (1) Heedless and Arrogant Approach: (ram the current policy through); (2) Weak and Feckless Approach: (try incremental reforms); (3) Dangerous and Demagogic Approach: (stripping the health bills of anything that might be unpopular and passing the rest regardless of the cost); and (4) Incoherent and Internecine Approach: (settling on no coherent policy but just blaming each other for cowardice and stupidity).

I am sure that variations on all four of these themes will be advocated by some members of Congress, I am also sure that Obama and the democrats can't walk away from passing at least some variant of healthcare reform legislation -- they will probably push for a watered-down version of the previous bill. However, I am personally just going to wait until some politician like Governor Rendell, or some of his  more ambitious colleagues, can take the time  to "explain" to me what I should think about all of this.

Definiens Takes Advantage of Social Media Sites for Marketing and CME

Dr. Keith Kaplan, who blogs over at Digital Pathology Blog recently alerted us to the fact that Definiens is taking advantage of social media like YouTube and Twitter to market their product as well as educate current and potential clients (see: Definiens on YouTube and Twitter):

Definiens has a channel on YouTube  (Definiens Life TV) hand a Twitter page. The YouTube page...has some excellent videos including several webinars you can view that have been uploaded in the past week. Another excellent example of Medicine 2.0.

Here's a brief description of Definiens copied from its web home page:

Automated Image Analysis: Definiens is the No.1 Enterprise Image Intelligence company. We support customers in analyzing and interpreting images on every scale, from microscopic cell structures to satellite images....At all powers of magnification, our technology enables customers to accomplish every task of image analysis, delivering deeper insights, faster results and better decisions.

I suspect that it's no accident that a relatively small digital pathology company like Definiens has been much quicker than, say, the large in-vitro diagnostic companies like Roche, Beckman Coulter, and Siemens, to understand the value of social media like YouTube and Twitter. I can only speculate about why this is so. Perhaps the executive leadership in the digital pathology companies is younger and more comfortable with the use of the social media. Perhaps they are attracted by the lower cost of viral marketing. Or perhaps they are more aware of the value of the digital videos posted on YouTube because "images" are an essential component of their business.

Webinars are a teaching resource that keep on giving after their initial creation because, as Definiens has quickly learned, they can be recorded and posted on Definiens Life TV for continuing training and eduction purposes. Recall that this is an era in which pathologists and medical technologists can watch YouTube videos at work with their smart phones. What a great opportunity to provide video's, for example, that can provide on-site specific guidance when troubleshooting problems with a laboratory instrument and perhaps avoid a service call.

Healthcare Reform and The Pressing Need to "Explain" the Proposed Legislation to the Average Joe

I have posted a number of of notes about healthcare reform but not lately (see: The Link Between Healthcare Reform and Post-Graduate Medical Training). For my money, the current draft of the legislation is primarily about health insurance reform and pork than anything else. My current malaise about this topic relates more to my chagrin aboout the political logrolling and lobbying rather than a lack of interest in reform (see: Health Insurers Emerge as Major Foes of Healthcare Reform; American Attitude toward Reform Through the Eyes of David Brooks). We are proceeding to the next "political" chapter because of the recent senatorial upset in Massachusetts with the election of a Republican to the slot and the new political calculations (see: After Massachusetts Senate defeat, Obama will need to adjust). However, I could feel my pulse racing yesterday when I read a quote from Ed Rendell, Governor of Pennsylvania, who said the following (see: Brown Win Forces Congress to Get 'Back to Basics'):

.... Americans oppose the health insurance changes because "the administration and its supporters, myself included, haven't done a good enough job explaining to people what's in this bill."

This is a perfect example of political gibberish and double-talk. Here's what I think Rendell is trying to say: There is nothing wrong with our political process. There is nothing wrong with all of the political lobbying that has distorted the original goals of this legislation. There is nothing wrong with the abilities of our elected politicians. There is nothing wrong with the draft of the legislation as it now stands. However, we politicians need to redouble our efforts to "explain" why the current legislation is optimal to the [stupid] electorate, many of whom have trouble with complex ideas and language.

Forging Stronger Diagnostic Links Between the Predisposition to Disease and Pre-Symptomatic Disease

Genomic testing will sometimes reveal a genetic predisposition to disease for an individual. This is both a strength and a weakness of this laboratory diagnostic approach because the person most frequently does not suffer from the actual disease. By way of contrast, serum biomarkers reveal the presence of disease, sometimes in a very early stage but, of course, provide only an indirect view of the genome (see: Wellness, Preventive Medicine, and the Classic Disease Model). This early stage view of disease provided by biomarkers is sometimes referred to as the pre-clinical or pre-disease stage. An individual exists in a state of wellness until a disease, sometimes in its early stage, is diagnosed. Predictive medicine takes advantage of various clinical lab tests (genomic, proteomic, and biomarkers, for example) to determine where a person falls on this continuous spectrum of wellness and disease. We look to the field of preventive medicine to take advantage of the numerous therapies known to medical science to forestall the onset of a disease or ameliorate its effects once it begins to take hold.

One of the criticisms of genomic testing is that it assesses a consumer/patient's predisposition to disease rather than the presence of early overt disease. Positive genomic test results are frequently a call for watchful waiting until such time as the disease that has revealed itself in the genome begins to manifest itself clinically. It understandable that some physicians and healthcare consumers alike shy away from such testing in that no therapeutic intervention is usually available or warranted as the result of such testing. It would be useful to develop more reliable links or relationships between genomic tests that indicate a predisposition to a disease and defined set of biomarkers that may provide definitive evidence that the early clinical stages of a disease have become manifest and may be treatable.

The need for such links is patently obvious to all physicians. What perhaps may be less obvious is how such links can be developed and then communicated to physicians or even to consumers who may want to take advantage of the genomic testing via the web sites that provide these services. The answer to this question is that a comprehensive set of genomic diagnostic tables need to be published on the web showing how a positive genomic test result can be confirmed by the measurement of individual or sets of serum biomarkers, the latter known as IVDMIAs. For the sake of this discussion, I will refer to such tables as genomic-biomarker interpretation tables (GBITs). Perhaps a reader of this blog can come up with a more suitable name.

The development of such tables is easier said than done because of the wide array of genomic tests and biomarkers that are available in the clinical lab market. Moreover, biomarkers are being described almost on a daily basis but the vast majority of them have never been validated in a clinical setting. Hence, the information that would be provided in such tables will need to be constantly updated. Moreover, such tables also need to be extensively annotated by physicians and lab scientists in order to accurately present the strengths and weakness of any conclusions that can be drawn from the information. The question of exactly what type of organizations would be tasked with the development of such tables will be the subject of subsequent notes. The GBIT authors and maintainers obviously need to be physicians and scientists free of any commercial biases.

Bariatric Surgery Moves into the Mainstream for Obesity Control

Weight loss surgery, also known as bariatric surgery, is rapidly transforming itself from a procedure scorned by mainstream medicine to a common procedure deemed to be effective for weight control. For some operated patients, it may also provide a cure for diseases like adult-onset diabetes (see: "Curing" Diabetes with Bariatric Surgery). This more positive view should probably not come as a surprise given our current epidemic of obesity that provides a stream of candidates for the operation and our growing familiarity with this type of intervention. A recent article in the LA Times provided a comprehensive description of bariatric surgery with a glimpse at how a new device may provide a new option for patients (see: Weight-loss surgery may soon be widely used). Below is an excerpt from it:

Advancements in procedures that are usually a last resort for the obese are making them potentially suitable for moderately overweight and diabetic people....Usually reserved for the most obese people, weight-loss surgery is unlikely to be a last-ditch option much longer. Technological advancements are turning it into a one-hour, incisionless procedure -- making it more attractive to moderately overweight adults...; overweight and obese teenagers; and normal-weight people with difficult-to-control diabetes. Several new procedures are already in human clinical trials....Many studies already attest to the effectiveness and increasing safety of the most popular weight-loss surgeries among morbidly obese people. Depending on the type of surgery used, patients lose 50% or more of their excess body weight and maintain that loss for as long as 10 years after surgery. In comparison, the most recent studies on long-term use of weight-loss medications show a typical weight loss of 5 to 22 pounds over one year with some side effects. Other research has found that bariatric surgery cures Type 2 diabetes in a majority of patients studied, as well as improving symptoms related to sleep apnea and heart disease, such as high cholesterol and blood pressure....The improvements in traditional bariatric surgery, combined with patient interest, have led to a surge in investigational new procedures, as well as discussions on whether more people could benefit from surgery....Furthest along in clinical trials is a noninvasive technique called TOGA, or transoral gastroplasty. In the procedure, a surgeon inserts a flexible tube through the mouth into the stomach and then uses staples to create a pouch that limits the amount of food that can be consumed....A previous small study showed that patients lost an average of almost 25 pounds after three months with no major complications reported. Long-term data aren't yet available.

I have posted a previous note about the LAP-BAND bariatric procedure (see: "Curing" Diabetes with Bariatric Surgery). It seems logical that new procedures such as TOGA are now being developed for weight loss (see: First U.S. incision-free procedure for obesity performed at Washington University). However, I do need to take issue with the author of the article quoted above who calls TOGA  "non-invasive" and describes it in the following way: a flexible tube [is inserted] through the mouth into the stomach and staples [are then  used] to create a pouch that limits the amount of food that can be consumed. Any procedure that limits the capacity of the stomach will have major metabolic consequences for a patient so that the post-operative management of such patients becomes critical. Obviously, the TOGA procedure is still in its early stages of development and it may eventually have distinct advantages over the LAP-BAND. However, only a small key-hole incision is required to install the the latter device and it has proved to be generally safe in the hands of experienced practitioners

More Discussion About the Possible Adverse Consequences of a Simple Breast Biopsy

In my blog note yesterday, I speculated about whether a simple diagnostic breast biopsy could, in and of itself, induce local inflammation and thereby simulate the invasion of a previously quiescent ductal carcinoma in-situ (DCIS) (see: Can a Simple Breast Biopsy Initiate Tissue Invasion by Intra-Ductal Cancer Cells?). Martin Trotter, a reader of this blog, responded with the following comment:

If DCIS is found on core biopsy then further surgery will be performed to remove the lesion. This surgery will also remove any "escaped DCIS" that resulted from the wound healing response to the previous biopsy. Time interval between biopsy and resection is short, so biological relevance of these "escaped" cells would likely be negligible. Just a thought.

Martin is referring to the fact that many women undergo lumpectomy following the diagnosis of intraductal carcinoma. Even if the inflammation following the initial diagnostic biopsy acts in some way to promote inflammation and stimulate the invasion of DCIS cells, the subsequent lumpectomy would remove the biopsy site as well as some of the surrounding breast parchenchyma. This second procedure would, in effect, excise the "cancer-promoting" inflamed tissue.

His question begins to delve into the question of the appropriate therapy following the diagnosis of DCIS. I did turn up one article on the web that seemed to me to be reliable (see: DCIS Treatment Options) and I quote from it. The initial treatment for DCIS is always surgery. There are two surgical approaches to DCIS treatment: lumpectomy, or a total mastectomy. If lumpectomy is chosen as the surgical method, the remainder of the breast is usually treated with radiation to minimize the chances of having a recurrence of DCIS in the breast. Radiation treatment is usually begun three to four weeks after the lumpectomy or when the wound has healed.

Let's assume that the patient in question selects total mastectomy. We can assume in this case that most of the breast tissue (and ducts) have been excised and that there will be little chance of the deleterious purported effects of post-operative inflammation. However, if the patient chooses lumpectomy, the inflammatory effects on the operated side could be exacerbated on the basis of both a biopsy and lumpectomy. I will assume that many DCIS's are multifocal. In this latter case, the assumption will probably be made that the post-lumpectomy radiation therapy is capable of mopping up the multifocal DCIS cells. I suspect that many of these lumpectomy patients are also treated with aromatase inhibitors (AI) which would suppress DCIS cell growth on both the operated side as well as in the contralateral breast.

Can a Simple Breast Biopsy Initiate Tissue Invasion by Intra-Ductal Cancer Cells?

Gina Kolata, the medical writer for the New York Times, recently discussed the theory that the normal cells surrounding a neoplastic lesion and the body's immuno-surveillance system can play a critical role in a tumor's invasive potential (see: Old Ideas Spur New Approaches in Cancer Fight). I have always believed this to be the case but this theory is now being taken more seriously in the research community. She cites a number of research studies that support this argument. One passage from her article relating to the possible adverse consequences of diagnostic breast biopsies caught my attention. I quote it  below:

[Dr. Kornelia Polyak of Harvard Medical School]thought [that] dangerous D.C.I.S. [ductal carcinoma in-situ] might have genes different from those of D.C.I.S. that remains harmlessly enclosed in milk ducts. Dangerous D.C.I.S. would look like invasive breast cancer cells and harmless D.C.I.S. would not. But, she found, D.C.I.S. cells looked just like cells from aggressive breast cancers — gene expression patterns, mutations and cell maturation patterns were all the same....“Why is it D.C.I.S. if it looks like invasive cancer?” She looked at cells surrounding D.C.I.S. The first thing she noticed was that when D.C.I.S. broke free of a milk duct, the duct’s outer layer had broken down. It could be that the duct falls apart because the cancer is bursting out. Or it could be that the cancer is escaping the duct because the outer layer disintegrated — which is what her research showed. As long as the milk duct is intact, D.C.I.S. cells cannot escape. She also found that when breast tissue is injured, wound healing can destroy the crucial outer layer of ducts, allowing D.C.I.S. to escape. That is what happens in animals, and it is her hypothesis that it happens in humans. It made her ask about biopsies. They are unavoidable, as she knows, because she recently had one herself. And they cannot be a huge factor in causing cancer or millions of women would be getting breast cancer at the site of their biopsies — and they are not. Still, she worries. “Frankly, this has not been studied extensively,” Dr. Polyak said. “People don’t like to bring it up.”

The question that is being asked above is whether a breast biopsy, initiated for the purpose of cancer diagnosis, can, in and of itself, promote the development of an invasive cancer on the basis of the inflammation and healing process that inexorably follows all biopsies. The basic idea is that these processes induce porosity of the basement membranes of breast ducts and enable the previously contained DCIS cells to escape into the surrounding tissue. Obviously, work will continue on this sequence of events to determine, first, whether this is a valid hypothesis and, second, whether the process can be blocked with, say, anti-inflammatory drugs. At the present time, breast biopsies are unavoidable because surgical pathology examination is the gold standard of breast diagnosis. However, in-situ techniques for the microscopic examination of tissue are rapidly being developed. Molecular imaging is also improving. All of these emerging diagnostic techniques may at some time be able to provide reliable diagnoses without disruption of the breast tissue.

Exhaled Aldehydes as Biomarkers for Lung Cancer

In the clinical pathology labs, the most common biologic sample undergoing analysis is clearly blood/serum. Probably following this, in order of frequency, would be urine and cells, the latter in the form of Pap smears. The analysis of exhaled gases in the labs would be considered unusual although not uncommon in law enforcement by the use of the breathalyzer for measuring blood alcohol content. It make good intuitive sense that volatile substances in exhaled breath could be representative of lung cell metabolism and that malignant cells growing in the lung could display a different metabolic pattern than normal cells. Hence a diagnostic opportunity.  A recent article raised the possibility that the analysis of exhaled breath would be useful to diagnose lung cancer (see: Breath gas aldehydes as biomarkers of lung cancer). Below is an excerpt from it, referring to a recent article by Fuchs et al. published in International Journal of Cancer:

There is experimental evidence that volatile substances in human breath can reflect presence of neoplasm. Lung cancer patients could be identified by means of exhaled pentanal, hexanal, octanal and nonanal concentrations. Exhaled aldehydes reflect aspects of oxidative stress and tumor-specific tissue composition and metabolism. Noninvasive recognition of lung malignancies may be realized if analytical skills, biochemical knowledge and medical expertise are combined into a joint effort.

• Exhaled C1-C10 aldehydes could be detected in all healthy volunteers, smokers and lung cancer patients
  
• Concentrations ranged from 7 pmol/l ...for butanal to 71 nmol/l...for formaldehyde
  
• Exhaled pentanal, hexanal, octanal and nonanal concentrations were significantly higher in lung cancer patients than in smokers and healthy controls
• Sensitivity and specificity of this method were comparable to the diagnostic certitude of conventional serum markers and CT imaging
• Lung cancer patients could be identified by means of exhaled pentanal, hexanal, octanal and nonanal concentrations

Prior to reading this report, I had not considered the inclusion of chemicals in exhaled breath within the range of commonly used cancer biomarkers. Obviously, this is only an early experimental report but I suppose that it's possible that it could lead to a breathalyzer-like device for monitoring smokers for the presence of a malignant lung neoplasm. For any scientifically valid health screening test to achieve wide use, it either needs to be integrated into the public consciousness as essential, like mammography, or it needs to be convenient. A "cancer-Breathalyzer" would certainly fall into this second category if additional research proves it to be a valid diagnostic tool. From my perspective, the avoidance of a venepuncture takes the convenience factor of a "cancer-Breathalyzer" device to a whole new level.

More Speculation About the Pathogenesis and Natural History of Endometriosis

In a recent note about endometriosis, I speculated about the pathogenesis of the lesion (see: Noted Scientist Puts New and Important Spotlight on Endometriosis). Dr. Mark Pool who blogs over at The Daily Sign-Out, responded with the following comment:

Wonderful post. We share a curiosity about this. I agree about the "retrograde-menstrual-flow theory" as being hogwash and regarded it as being about as "scientific" as UFO/alien visitations from the 50s/60s. More biologically sound is the idea about metaplasia. But what (to me, anyway, is more intriguing is how the metaplastic epithelium induces the stroma around it to become endometrial-like stroma or is the "stroma" just another metaplastic change. Also, what of the association between endometriosis and a range of neoplastic lesions?

Mark raises some interesting issues in his short comment. If the readers of this blog will indulge me, I will set off on a brief excursion into some pathologic esoterica. Under the microscope, endometriosis consists of endometrial glands surrounding by endometrial-like stroma. The question arises whether this stroma represents a metaplasia of the pre-existing garden-variety stroma induced by the endometrial glands. Although Mark does not raise the issue, it's also possible, I think, that the columnar endometrial epithelial cells undergo another type of metaplasia into spindled stromal cells. Such a suggestion is a form of heresy in that many of us were taught that mesenchymal cells are inert and fundamentally different than the dynamic epithelial cells. In other words, epithelial cells don't morph into stromal cells or stromal-like spindled cells.

Mark also raises the issue of whether some forms of endometriosis are pre-cancerous. I did a little snooping around and came up with the following passage from Clinical Obstetrics and Gynaecology:

For several decades, endometriosis has been suspected of playing a role in the aetiology of ovarian cancer....Epidemiological evidence from large-cohort studies confirms endometriosis as an independent risk factor for ovarian cancer. Further circumstantial evidence for this link was found in the common risk factors for ovarian cancer and endometriosis. These risk factors influence retrograde menstruation and endometriosis in the same positive or negative way. Based on data in the literature, the prevalence of endometriosis in epithelial ovarian cancer has been calculated to be 4.5, 1.4, 35.9, and 19.0% for serous, mucinous, clear-cell and endometrioid ovarian carcinoma, respectively. The risk of malignant transformation in ovarian endometriosis was calculated at 2.5% but this might be an underestimate. In addition, some authors described atypical endometriosis in a spatial and chronological association with ovarian cancer. Finally, molecular studies have detected common alterations in endometriosis and ovarian cancer. These data suggest that some tumours, especially endometrioid and clear-cell carcinomas, can arise from endometriosis. Moreover, endometriosis-associated ovarian cancer represents a distinct clinical entity, with a more favourable biological behaviour, given a lower stage distribution and better survival than non-endometriosis-associated ovarian cancer.

To close the loop, here's a link to an article about atypical endometriosis (see: Atypical endometriosis: a clinicopathologic study of 163 cases). So, some forms of endometriosis are much more than a nuisance -- they can rarely set the stage for an ovarian cancer, although one that behaves less aggressively than other types.

The Role of CRP Testing in the Initiation of Treatment with Crestor

The Harvard Health Letter recently published an article about the top ten health stories of 2009 (see: The top 10 health stories of 2009). One of the ten items focused on the value of C-reactive protein (CRP) testing so I thought that it would be useful to repeat this item here. Below is the passage from the article:

CRP: Ready to make an entrance? Late in 2008, results from the industry-funded JUPITER trial showed that people with normal LDL cholesterol levels (less than 130 mg/dL) but relatively high CRP levels (2 mg/L or higher) could cut their risk of having a heart attack or stroke in half by taking a high dose (20 mg) of a powerful statin drug, rosuvastatin (Crestor). CRP stands for C-reactive protein....Statin drugs are taken primarily to lower LDL levels, but this was added proof that they also calm inflammation. That first round of JUPITER results made a big splash, but it left room for debate about how CRP testing and lowering should fit into cardiovascular care. Subanalyses of the JUPITER data published in Lancet helped clarify if not completely settle matters. People in the trial who reached a very low LDL level (less than 70 mg/dL) cut their risk of having a cardiovascular "event"...by 55%. But those who achieved a sub-70 LDL and a CRP of less than 2 mg/L lowered their risk by 65%. And reaching a CRP of less than 1 mg/L lowered it by 79%. Many unanswered questions remain. What are the long-term consequences of taking high doses of potent statins like rosuvastatin? Might changes in diet, or increased physical activity, achieve the same thing? Still, the JUPITER results add to the evidence showing that cardiovascular disease is fundamentally an inflammatory process. The official LDL-centric guidelines haven't changed, but many doctors are going ahead and ordering CRP tests for their patients with cardiac risk factors, even if their LDL levels are normal. If two tests show the CRP level is high, they may prescribe a high dose of a potent statin.

Statins seem to have an anti-inflammatory effect, inflammation of the coronary arteries may have a causal effect in cardiovascular events, and CRP is a biomarker for inflammation anywhere in the body. Hence and for patients with cardiac risk factors such as being overweight or hypertensive, treatment with statins may be initiated even in the face of normal LDL levels. Measurement of CRP is certainly not novel or new. Why, then, does this "top ten" article describe CRP as ready to make an entrance. I think that the key point being made is that, as the results of the original JUPITER study and subanalyses are disseminated, a high CRP level has now become an actionable lab test for physicians and an effective drug, Crestor, is readily available to treat coronary artery inflammation.